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1
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Cao NT, Cha GS, Kim JH, Lee Y, Yun CH, Nguyen NA. Production of an O-desmethylated product, a major human metabolite, of rabeprazole sulfide by bacterial P450 enzymes. Enzyme Microb Technol 2023; 171:110328. [PMID: 37751627 DOI: 10.1016/j.enzmictec.2023.110328] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/03/2023] [Revised: 08/28/2023] [Accepted: 09/18/2023] [Indexed: 09/28/2023]
Abstract
Rabeprazole is a common type of proton pump inhibitor (PPI) used to treat various peptic disorders. Unlike most PPI drugs, rabeprazole is spontaneously reduced to rabeprazole sulfide (thioether) when it is given to patients. As a result, rabeprazole sulfide is considered one of the active metabolites of rabeprazole. Rabeprazole sulfide is mainly metabolized to desmethyl rabeprazole sulfide by CYP2C19 and CYP2D6 in people. However, the pharmacological efficacy and safety of desmethyl rabeprazole sulfide have not yet been investigated. Its usage is challenging due to the high cost associated with the drug. In this study, we found CYP102A1 mutants that can produce desmethyl rabeprazole sulfide as a major metabolite of rabeprazole sulfide. The chemical characteristics of the major product were confirmed using high-performance liquid chromatography, LC-mass spectrometry, and nuclear magnetic resonance spectroscopy. CYP102A1 mutants R47L/F87V/L188Q, R47L/F87V/L188Q/A335V/Q359R, and R47L/F87V/L188Q/I254V/D351E showed kcat values of 39, 93, and 88 min-1, respectively, for O-desmethylation of rabeprazole sulfide. Furthermore, the highest concentration of desmethyl rabeprazole sulfide product from 2 mM rabeprazole sulfide at optimal conditions was obtained in bacterial whole-cell biotransformation with the R47L/F87V/L188Q mutant, reaching 0.63 mM at 4-h incubation. In conclusion, we present a platform that facilitates the efficient and sustainable production of the desmethylated product from rabeprazole sulfide for use in the biopharmaceutical industry.
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Affiliation(s)
- Ngoc Tan Cao
- School of Biological Sciences and Technology, Chonnam National University, 77 Yongbongro, Gwangju 61186, Republic of Korea
| | - Gun Su Cha
- Namhae Garlic Research Institute, 2465-8 Namhaedaero, Gyeongsangnamdo 52430, Republic of Korea
| | - Jeong-Hoon Kim
- School of Biological Sciences and Biotechnology, Graduate School, Chonnam National University, 77 Yongbongro, Gwangju 61186, Republic of Korea
| | - Yujin Lee
- School of Biological Sciences and Biotechnology, Graduate School, Chonnam National University, 77 Yongbongro, Gwangju 61186, Republic of Korea
| | - Chul-Ho Yun
- School of Biological Sciences and Technology, Chonnam National University, 77 Yongbongro, Gwangju 61186, Republic of Korea.
| | - Ngoc Anh Nguyen
- School of Biological Sciences and Technology, Chonnam National University, 77 Yongbongro, Gwangju 61186, Republic of Korea.
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2
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Liu Y, Ma L, Cheng J, Su J. Effects of Omeprazole on Recurrent Clostridioides difficile Infection Caused by ST81 Strains and Their Potential Mechanisms. Antimicrob Agents Chemother 2023; 67:e0022123. [PMID: 37223895 PMCID: PMC10269155 DOI: 10.1128/aac.00221-23] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/22/2023] [Accepted: 04/12/2023] [Indexed: 05/25/2023] Open
Abstract
Clostridioides difficile infection (CDI) is associated with high recurrence rates that have substantial effects on patients' quality of life. To investigate the risk factors and potential mechanisms contributing to recurrent CDI (rCDI), a total of 243 cases were enrolled in this study. The history of omeprazole (OME) medication and ST81 strain infection were considered the two independent risks with the highest odds ratios in rCDI. In the presence of OME, we detected concentration-dependent increases in the MIC values of fluoroquinolone antibiotics against ST81 strains. Mechanically, OME facilitated ST81 strain sporulation and spore germination by blocking the pathway of purine metabolism and also promoted an increase in cell motility and toxin production by turning the flagellar switch to the ON state. In conclusion, OME affects several biological processes during C difficile growth, which have fundamental impacts on the development of rCDI caused by ST81 strains. Programmed OME administration and stringent surveillance of the emerging ST81 genotype are matters of considerable urgency and significance in rCDI prevention.
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Affiliation(s)
- Yifeng Liu
- Clinical Laboratory Center, Beijing Friendship Hospital, Capital Medical University, Beijing, China
| | - Liyan Ma
- Clinical Laboratory Center, Beijing Friendship Hospital, Capital Medical University, Beijing, China
| | - Jingwei Cheng
- Clinical Laboratory Center, Beijing Friendship Hospital, Capital Medical University, Beijing, China
| | - Jianrong Su
- Clinical Laboratory Center, Beijing Friendship Hospital, Capital Medical University, Beijing, China
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3
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Tang C, Li L, Ma X, Wang J, Chen B, Dai X, Zhang Y, Chen X. Qualitative and quantitative determination of anaprazole and its major metabolites in human plasma. J Pharm Biomed Anal 2020; 183:113146. [PMID: 32086126 DOI: 10.1016/j.jpba.2020.113146] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/09/2019] [Revised: 12/30/2019] [Accepted: 02/04/2020] [Indexed: 12/11/2022]
Abstract
Anaprazole is a novel proton pump inhibitor under development for the treatment of gastric and duodenal ulcers. In the present study, an ultra-performance liquid chromatography-ultraviolet detector/quadrupole time-of-flight mass spectrometry method was developed for the metabolic profiling of human plasma after an oral administration of 40 mg anaprazole. The principal metabolic pathways were identified as sulfoxide reduction to thioether (M8-1), dehydrogenation (M21-1), sulfoxide oxidation to sulfone (M16-3), and sulfoxide reduction with O-demethylation to form carboxylic acid (M7-1). Anaprazole, M8-1, M16-3, M21-1, and M7-1 were selected and further quantified in human plasma by using a rapid and sensitive liquid chromatography-tandem mass spectrometry method. Anaprazole and its four metabolites were extracted from 50 of μL plasma by acetonitrile protein precipitation. Chromatographic retention and separation were achieved on an Kinetex XB-C18 column (50 mm × 4.6 mm i.d., 5 μm) under gradient elution using 5 mM ammonium acetate with 0.005 % ammonium hydroxide and methanol with 0.005 % ammonium hydroxide as the mobile phase. Positive electrospray ionization was performed using multiple reaction monitoring with transitions of m/z 402.2→242.2, 386.2→226.2, 400.2→242.2, 418.2→282.2, and 386.2→161.2 for anaprazole, M8-1, M21-1, M16-3, and M7-1, respectively. This method was linear in the range of 5.00-3000 ng/mL for anaprazole and 1.00-600 ng/mL for the four metabolites. The lower limit of quantitation was established at 5.00 ng/mL for anaprazole and 1.00 ng/mL for the metabolites. The quantitative method was used to evaluate the pharmacokinetics of anaprazole in phase I clinical trials.
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Affiliation(s)
- Chongzhuang Tang
- Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 501 Haike Road, Shanghai, 201203, China; University of Chinese Academy of Sciences, No.19A Yuquan Road, Beijing, 100049, China
| | - Liang Li
- Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 501 Haike Road, Shanghai, 201203, China
| | - Xifeng Ma
- XuanZhu Pharma, 2518 Tianchen Street, Jinan, Shandong, China
| | - Jin Wang
- XuanZhu Pharma, 2518 Tianchen Street, Jinan, Shandong, China
| | - Bo Chen
- XuanZhu Pharma, 2518 Tianchen Street, Jinan, Shandong, China
| | - Xiaojian Dai
- Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 501 Haike Road, Shanghai, 201203, China
| | - Yifan Zhang
- Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 501 Haike Road, Shanghai, 201203, China
| | - Xiaoyan Chen
- Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 501 Haike Road, Shanghai, 201203, China; University of Chinese Academy of Sciences, No.19A Yuquan Road, Beijing, 100049, China.
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4
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Surur AS, Schulig L, Link A. Interconnection of sulfides and sulfoxides in medicinal chemistry. Arch Pharm (Weinheim) 2018; 352:e1800248. [DOI: 10.1002/ardp.201800248] [Citation(s) in RCA: 25] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/22/2018] [Revised: 10/29/2018] [Accepted: 10/30/2018] [Indexed: 12/17/2022]
Affiliation(s)
| | - Lukas Schulig
- Institute of Pharmacy; University of Greifswald; Greifswald Germany
| | - Andreas Link
- Institute of Pharmacy; University of Greifswald; Greifswald Germany
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The Impact of Efflux Pump Inhibitors on the Activity of Selected Non-Antibiotic Medicinal Products against Gram-Negative Bacteria. Molecules 2017; 22:molecules22010114. [PMID: 28085074 PMCID: PMC6155833 DOI: 10.3390/molecules22010114] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/12/2016] [Revised: 12/12/2016] [Accepted: 01/04/2017] [Indexed: 11/22/2022] Open
Abstract
The potential role of non-antibiotic medicinal products in the treatment of multidrug-resistant Gram-negative bacteria has recently been investigated. It is highly likely that the presence of efflux pumps may be one of the reasons for the weak activity of non-antibiotics, as in the case of some non-steroidal anti-inflammatory drugs (NSAIDs), against Gram-negative rods. The activity of eight drugs of potential non-antibiotic activity, active substance standards, and relevant medicinal products were analysed with and without of efflux pump inhibitors against 180 strains of five Gram-negative rod species by minimum inhibitory concentration (MIC) value determination in the presence of 1 mM MgSO4. Furthermore, the influence of non-antibiotics on the susceptibility of clinical strains to quinolones with or without PAβN (Phe-Arg-β-naphthylamide) was investigated. The impacts of PAβN on the susceptibility of bacteria to non-antibiotics suggests that amitriptyline, alendronate, nicergoline, and ticlopidine are substrates of efflux pumps in Gram-negative rods. Amitriptyline/Amitriptylinum showed the highest direct antibacterial activity, with MICs ranging 100–800 mg/L against all studied species. Significant decreases in the MIC values of other active substances (acyclovir, atorvastatin, and famotidine) tested with pump inhibitors were not observed. The investigated non-antibiotic medicinal products did not alter the MICs of quinolones in the absence and in the presence of PAβN to the studied clinical strains of five groups of species.
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Andreev DN, Dicheva DT, Maev IV. [Possibilities for optimization of eradication therapy for Helicobacter pylori infection in modern clinical practice]. TERAPEVT ARKH 2017; 89:84-90. [PMID: 28393827 DOI: 10.17116/terarkh201789284-90] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 07/28/2024]
Abstract
A steady decline in the effectiveness of standard eradication therapy (ET) regimens for Helicobacter pylori infection necessitates a search for ways of their optimization, by enhancing the efficiency of treatment protocols and by improving their safety and tolerability. The review systematizes the data available in the literature on main accessible methods for optimizing ET regimens. Among the optimization methods that can considerably enhance the efficiency of ET regimens, one may identify their addition of a bismuth agent (by 10-20%), the use of rebamipide (by 11.9%), adjuvant therapy with probiotics (by 8.1-13%), or double-dose proton pump inhibitors (by 8%). Only adjuvant therapy with probiotics results in a significant decrease in the incidence of side effects from ET. In posteradication period, rebamipide should be used to potentiate gastric mucosal repair and to regress inflammatory processes.
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Affiliation(s)
- D N Andreev
- A.I. Evdokimov Moscow State University of Medicine and Dentistry, Ministry of Health of Russia, Moscow, Russia
| | - D T Dicheva
- A.I. Evdokimov Moscow State University of Medicine and Dentistry, Ministry of Health of Russia, Moscow, Russia
| | - I V Maev
- A.I. Evdokimov Moscow State University of Medicine and Dentistry, Ministry of Health of Russia, Moscow, Russia
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7
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Feng X, Zhu W, Schurig-Briccio LA, Lindert S, Shoen C, Hitchings R, Li J, Wang Y, Baig N, Zhou T, Kim BK, Crick DC, Cynamon M, McCammon JA, Gennis RB, Oldfield E. Antiinfectives targeting enzymes and the proton motive force. Proc Natl Acad Sci U S A 2015; 112:E7073-82. [PMID: 26644565 PMCID: PMC4697371 DOI: 10.1073/pnas.1521988112] [Citation(s) in RCA: 116] [Impact Index Per Article: 11.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/21/2022] Open
Abstract
There is a growing need for new antibiotics. Compounds that target the proton motive force (PMF), uncouplers, represent one possible class of compounds that might be developed because they are already used to treat parasitic infections, and there is interest in their use for the treatment of other diseases, such as diabetes. Here, we tested a series of compounds, most with known antiinfective activity, for uncoupler activity. Many cationic amphiphiles tested positive, and some targeted isoprenoid biosynthesis or affected lipid bilayer structure. As an example, we found that clomiphene, a recently discovered undecaprenyl diphosphate synthase inhibitor active against Staphylococcus aureus, is an uncoupler. Using in silico screening, we then found that the anti-glioblastoma multiforme drug lead vacquinol is an inhibitor of Mycobacterium tuberculosis tuberculosinyl adenosine synthase, as well as being an uncoupler. Because vacquinol is also an inhibitor of M. tuberculosis cell growth, we used similarity searches based on the vacquinol structure, finding analogs with potent (∼0.5-2 μg/mL) activity against M. tuberculosis and S. aureus. Our results give a logical explanation of the observation that most new tuberculosis drug leads discovered by phenotypic screens and genome sequencing are highly lipophilic (logP ∼5.7) bases with membrane targets because such species are expected to partition into hydrophobic membranes, inhibiting membrane proteins, in addition to collapsing the PMF. This multiple targeting is expected to be of importance in overcoming the development of drug resistance because targeting membrane physical properties is expected to be less susceptible to the development of resistance.
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Affiliation(s)
- Xinxin Feng
- Department of Chemistry, University of Illinois, Urbana, IL 61801
| | - Wei Zhu
- Department of Chemistry, University of Illinois, Urbana, IL 61801
| | | | - Steffen Lindert
- Department of Chemistry and Biochemistry, Ohio State University, Columbus, OH 43210
| | - Carolyn Shoen
- Central New York Research Corporation, Veterans Affairs Medical Center, Syracuse, NY 13210
| | - Reese Hitchings
- Department of Microbiology, Immunology, and Pathology, Colorado State University, Fort Collins, CO 80523
| | - Jikun Li
- Department of Chemistry, University of Illinois, Urbana, IL 61801
| | - Yang Wang
- Department of Chemistry, University of Illinois, Urbana, IL 61801
| | - Noman Baig
- Department of Chemistry, University of Illinois, Urbana, IL 61801
| | - Tianhui Zhou
- Department of Chemistry, University of Illinois, Urbana, IL 61801
| | - Boo Kyung Kim
- Department of Chemistry, University of Illinois, Urbana, IL 61801
| | - Dean C Crick
- Department of Microbiology, Immunology, and Pathology, Colorado State University, Fort Collins, CO 80523
| | - Michael Cynamon
- Central New York Research Corporation, Veterans Affairs Medical Center, Syracuse, NY 13210
| | - J Andrew McCammon
- Department of Pharmacology and Department of Chemistry & Biochemistry, University of California San Diego, La Jolla, CA 92093; Howard Hughes Medical Institute, University of California San Diego, La Jolla, CA 92093; National Biomedical Computation Resource, University of California San Diego, La Jolla, CA 92093;
| | - Robert B Gennis
- Department of Chemistry, University of Illinois, Urbana, IL 61801; Department of Biochemistry, University of Illinois, Urbana, IL 61801; Center for Biophysics and Computational Biology, University of Illinois at Urbana-Champaign, Urbana, IL 61801
| | - Eric Oldfield
- Department of Chemistry, University of Illinois, Urbana, IL 61801; Center for Biophysics and Computational Biology, University of Illinois at Urbana-Champaign, Urbana, IL 61801
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8
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Lu C, Jia Y, Song Y, Li X, Sun Y, Zhao J, Wang S, Shi L, Wen A, Ding L. Application of a liquid chromatographic/tandem mass spectrometric method to a urinary excretion study of rabeprazole and two of its metabolites in healthy human urine. J Chromatogr B Analyt Technol Biomed Life Sci 2015; 988:75-80. [DOI: 10.1016/j.jchromb.2015.01.023] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/05/2014] [Revised: 01/14/2015] [Accepted: 01/18/2015] [Indexed: 10/24/2022]
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Adachi K, Hashimoto T, Ishihara S, Fujishiro H, Sato S, Sato H, Amano Y, Hattori S, Kinoshita Y. Comparison of five-day Helicobacter pylori eradication regimens: rabeprazole-based and omeprazole-based regimens with and without omeprazole pretreatment. Curr Ther Res Clin Exp 2014; 64:412-21. [PMID: 24944392 DOI: 10.1016/s0011-393x(03)00120-6] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 05/21/2003] [Indexed: 12/20/2022] Open
Abstract
BACKGROUND The onset of antisecretory activity of rabeprazole is faster than that of omeprazole. OBJECTIVE This study was performed to compare the efficacy of short-term rabeprazole-based triple therapy with that of omeprazole-based triple therapy and to determine the influence of omeprazole pretreatment in omeprazole-based short-term triple therapy. METHODS This was a 2-center, open-label, prospective, randomized study. Patients who tested positive for Helicobacter (formerly Campylobacter) pylori were randomized to one of three 5-day regimens: (1) rabeprazole 20 mg BID, amoxicillin 500 mg TID, and clarithromycin 400 mg BID (RAC group); (2) omeprazole 20 mg BID, amoxicillin 500 mg TID, and clarithromycin 400 mg BID without omeprazole pretreatment (OAC1 group); and (3) omeprazole 20 mg BID, amoxicillin 500 mg TID, and clarithromycin 400 mg BID with 5 days of omeprazole pretreatment 20 mg BID (OAC2 group). Eradication was assessed by (13)C-urea breath test and rapid urease test ∼1 month after completion of treatment. All patients who entered this study were included in the intent-to-treat (ITT) analysis, patients who completed the study were included in the per-protocol (PP) analysis, and patients who did not undergo the (13)C-urea breath test and rapid urease test were included in the all-patients-treated (APT) analysis. RESULTS A total of 120 patients (86 men, 34 women; mean [SD] age, 55.8 [14.3] years; range, 19-86 years) were assigned to the RAC, OAC1, or OAC2 group (40 patients in each group). ITT, PP, and APT eradication rates in the RAC group were 90%, 92%, and 90%, respectively; in the OAC1 group, 75%, 83%, and 75%; and in the OAC2 group, 85%, 90%, and 87%. These eradication rates were not significantly different between groups. CONCLUSIONS Eradication rates did not differ significantly between the three 5-day proton pump inhibitor-based triple therapies in this study population. However, 5-day rabeprazole-based triple therapy tends to be more effective than 5-day omeprazole-based triple therapy in the eradication of H pylori, and treatment with omeprazole before eradication therapy may improve the eradication rates of 5-day omeprazole-based therapy.
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Affiliation(s)
- Kyoichi Adachi
- Second Department of Internal Medicine, Shimane Medical University, Shimane, Japan
| | | | - Shunji Ishihara
- Second Department of Internal Medicine, Shimane Medical University, Shimane, Japan
| | - Hirofumi Fujishiro
- Second Department of Internal Medicine, Shimane Medical University, Shimane, Japan
| | - Shuichi Sato
- Second Department of Internal Medicine, Shimane Medical University, Shimane, Japan
| | - Hiroshi Sato
- Second Department of Internal Medicine, Shimane Medical University, Shimane, Japan
| | - Yuji Amano
- Department of Gastrointestinal Endoscopy, Shimane Medical University, Shimane, Japan
| | - Shuzo Hattori
- Department of Internal Medicine, Unnan General Hospital, Shimane, Japan
| | - Yoshikazu Kinoshita
- Second Department of Internal Medicine, Shimane Medical University, Shimane, Japan
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Iwao Y, Takano T, Taneike I, Reva I, Isobe H, Zhang HM, Nishiyama A, Yamamoto T. Anti-Helicobacter pylori actions of CV-6209, a platelet-activating factor receptor antagonist. J GEN APPL MICROBIOL 2014; 59:147-52. [PMID: 23759868 DOI: 10.2323/jgam.59.147] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/03/2022]
Affiliation(s)
- Yasuhisa Iwao
- Division of Bacteriology, Department of Infectious Disease Control and International Medicine, Niigata University Graduate School of Medical and Dental Sciences, Niigata 951-8510, Japan
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Smoking, Proton Pump Inhibitors and Antibiotic Administration as Factors Affecting Direct Screening of Helicobacter Pylori Infection Among Patients With Dyspepsia. ARCHIVES OF CLINICAL INFECTIOUS DISEASES 2014. [DOI: 10.5812/archcid.15774] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
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12
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Yamamoto T, Takano T, Higuchi W, Hung WC, Reva I, Yabe S, Iwao Y, Khokhlova O. Unique features of the motility and structures in the flagellate polar region of Campylobacter jejuni and other species: an electron microscopic study. Microbiol Immunol 2013; 57:83-90. [PMID: 23252968 DOI: 10.1111/1348-0421.12013] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/19/2012] [Revised: 07/13/2012] [Accepted: 10/14/2012] [Indexed: 11/28/2022]
Abstract
Similarly to Helicobacter pylori but unlike Vibrio cholerae O1/O139, Campylobacter jejuni is non-motile at 20°C but highly motile at ≥37°C. The bacterium C. jejuni has one of the highest swimming speeds reported (>100 μm/s), especially at 42°C. Straight and spiral bacterial shapes share the same motility. C. jejuni has a unique structure in the flagellate polar region, which is characterized by a cup-like structure (beneath the inner membrane), a funnel shape (opening onto the polar surface) and less dense space (cytoplasm). Other Campylobacter species (coli, fetus, and lari) have similar motility and flagellate polar structures, albeit with slight differences. This is especially true for Campylobacter fetus, which has a flagellum only at one pole and a cup-like structure composed of two membranes.
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Affiliation(s)
- Tatsuo Yamamoto
- Division of Bacteriology, Department of Infectious Disease Control and International Medicine, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan. ‐u.ac.jp
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Le Moal VL, Fayol-Messaoudi D, Servin AL. Compound(s) secreted by Lactobacillus casei strain Shirota YIT9029 irreversibly and reversibly impair the swimming motility of Helicobacter pylori and Salmonella enterica serovar Typhimurium, respectively. MICROBIOLOGY-SGM 2013; 159:1956-1971. [PMID: 23873784 DOI: 10.1099/mic.0.067678-0] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
We conducted experiments in order to examine whether the probiotic Lactobacillus casei strain Shirota YIT9029 (LcS) in vitro and in vivo antagonism of Helicobacter pylori and Salmonella, involves inhibition of the swimming motility of these pathogens. We report the irreversible inhibition of the swimming motility of H. pylori strain 1101 and reversible inhibition of Salmonella enterica serovar Typhimurium (S. Typhimurium) strain SL1344 by compound(s) secreted by LcS. In H. pylori 1101, irreversible inhibition results in the helical cells being progressively replaced by cells with 'c'-shaped and coccoid morphologies, accompanied by a loss of FlaA and FlaB flagellin expression. In S. Typhimurium SL1344, transient inhibition develops after membrane depolarization and without modification of expression of FliC flagellin. The inhibitory activity of strain LcS against both S. Typhimurium and H. pylori swimming motilities is linked with a small sized, heat-sensitive, and partially trypsin-sensitive, secreted compound(s), and needed the cooperation of the secreted membrane permeabilizing lactic acid metabolite. The inhibition of S. Typhimurium SL1344 swimming motility leads to delayed cell entry into human enterocyte-like Caco-2/TC7 cells and a strong decrease of cell entry into human mucus-secreting HT29-MTX cells.
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Affiliation(s)
- Vanessa Liévin Le Moal
- Faculté de Pharmacie, Université Paris-Sud, Châtenay-Malabry 92296, France.,UMR 8076 (BioCIS), CNRS, Faculté de Pharmacie, Université Paris-Sud, Châtenay-Malabry 92296, France
| | - Domitille Fayol-Messaoudi
- Faculté de Pharmacie, Université Paris-Sud, Châtenay-Malabry 92296, France.,UMR 8076 (BioCIS), CNRS, Faculté de Pharmacie, Université Paris-Sud, Châtenay-Malabry 92296, France
| | - Alain L Servin
- Faculté de Pharmacie, Université Paris-Sud, Châtenay-Malabry 92296, France.,UMR 8076 (BioCIS), CNRS, Faculté de Pharmacie, Université Paris-Sud, Châtenay-Malabry 92296, France
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14
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Reduction of overall Helicobacter pylori colonization levels in the stomach of Mongolian gerbil by Lactobacillus johnsonii La1 (LC1) and its in vitro activities against H. pylori motility and adherence. Biosci Biotechnol Biochem 2012; 76:850-2. [PMID: 22484956 DOI: 10.1271/bbb.110921] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
The effects of Lactobacillus johnsonii La1 (LC1) on Helicobacter pylori colonization in the stomach were investigated. H. pylori colonization and gastritis in LC1-inoculated Mongolian gerbils were significantly less intense than those in the control animals. LC1 culture supernatant (>10-kDa fraction) inhibited H. pylori motility and induced bacterial aggregation in human gastric epithelial cells, suggesting the potential of clinical use of LC1 product.
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15
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Emergence of NDM-1-positive capsulated Escherichia coli with high resistance to serum killing in Japan. J Infect Chemother 2011; 17:435-9. [PMID: 21437680 DOI: 10.1007/s10156-011-0232-3] [Citation(s) in RCA: 27] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/28/2010] [Accepted: 02/09/2011] [Indexed: 10/18/2022]
Abstract
The New Delhi metallo-β-lactamase-1 (NDM-1) gene, bla (NDM-1), is an emerging plasmid-borne drug resistance gene, which encodes for exceptionally broad-spectrum β-lactamase, being able to hydrolyze a wide variety of β-lactams, including carbapenems, and was first reported in Klebsiella pneumoniae from a Swedish patient of Indian origin in 2009. It is widely distributed among Enterobacteriacae and has geographically exhibited extremely rapid and global spread. In this study, we characterized the bla (NDM-1)-positive ST38 Escherichia coli strain NDM-1 Dok01 (which was isolated from the blood of a 54-year-old Japanese inpatient, who had previously visited India), focusing on bacterial surface structures related to virulence. The E. coli culture contained colony variants, which developed a transparent smooth colony and a rough colony on blood agar plates. The smooth colony-forming cells (substrain M1) possessed a surface capsule and were resistant to serum killing, whereas rough colony-forming mutants (substrain B2) lacked a capsule (and a 5.3-kb plasmid) and were highly susceptible to serum killing. Reflecting the surface structural difference, substrain M1 was more flagellated and motile, whereas substrain B2 was less flagellated and apparently possessed straight pili 5 nm wide, which played a role in adherence to human intestinal cells and bacterial autoaggregation. Data suggest that the bla (NDM-1)-positive ST38 E. coli has emerged in Japan and that it is a capsulated bacterial pathogen with virulence potential in the blood stream.
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16
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[Evidence and uncertainties on the clinical use of proton pump inhibitors]. GASTROENTEROLOGIA Y HEPATOLOGIA 2010; 33 Suppl 1:5-10. [PMID: 20728783 DOI: 10.1016/s0210-5705(10)70002-9] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/23/2022]
Abstract
Proton pump inhibitors (PPI) are the most potent and effective drugs for the control of gastric acid secretion and constitute one of the most widely prescribed pharmacological groups worldwide. The safety and efficacy of PPI have been demonstrated in clinical practice and these drugs are currently the treatment of choice in peptic ulcer diseases, Helicobacter pylori infection, gastroesophageal reflux disease, nonsteroidal antiinflammatory drug gastropathy and functional dyspepsia. However, despite the excellent pharmacological profile of current PPI, their rapidity of action may be insufficient in some diseases, 24-hour acid inhibition is not always achieved and - to a greater or lesser extent depending on the distinct molecules of the PPI - there is interindividual variability in gastric antisecretory efficacy, depending on genetic polymorphism of CYP2C19, which could affect individual metabolism of the distinct PPI. New generations of these drugs will probably eliminate these deficiencies.
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Kuo CH, Wang SSW, Hsu WH, Kuo FC, Weng BC, Li CJ, Hsu PI, Chen A, Hung WC, Yang YC, Wang WM, Wu DC. Rabeprazole can overcome the impact of CYP2C19 polymorphism on quadruple therapy. Helicobacter 2010; 15:265-272. [PMID: 20633187 DOI: 10.1111/j.1523-5378.2010.00761.x] [Citation(s) in RCA: 29] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
OBJECTIVES The prospective study was designed to clarify the impact of CYP2C19 on quadruple therapies and survey the efficacies of rabeprazole-based quadruple therapy for Helicobacter pylori infection after failure of standard triple therapies. PATIENTS AND METHODS From January 2007 to March 2009, 1055 H. pylori-infected patients received standard triple regimens (proton-pump inhibitor (PPI), clarithromycin, and amoxicillin). Helicobacter pylori eradication was achieved in 865 (81.9%) subjects. One hundred ninety eradication-failure patients were enrolled and randomly assigned to receive a 7-day eradication therapy. Ninety-six patients were treated with esomeprazole-based quadruple rescue therapies (EB), while 94 patients were treated with rabeprazole-based quadruple rescue therapies (RB). Follow-up endoscopy was done 16 weeks later to assess the treatment response. Patients' responses, CYP2C19 genotypes, and antibiotics resistances were also examined. RESULTS Intention-to-treat analysis revealed that RB had better eradication rates than EB (EB: 72.9%; 95% CI: 64.9-80.9% and RB: 78.7%; 95% CI 72.5-84.9%) (p value = .543). Per-protocol results were EB = 75.3%; 95% CI: 70.3-80.3% and RB = 85.1%; 95% CI: 80.6-89.6% (p value = .0401). Both regimens had similar compliance (p value = 0.155) and adverse events (p value = 0.219). We also surveyed those patients without resistance of any antibiotics. RB still showed better outcome than EB. Our data showed that esomeprazole-based regimen and CYP2C19 Hom EM genotype were important predictors for eradication failure. CONCLUSIONS In quadruple therapy, rabeprazole-based regimens had better efficacy than esomeprazole-based regimens. CYP2C19 polymorphism also played an important role in quadruple therapy. It seems advisable to change PPI to rabeprazole in second-line quadruple therapy.
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Affiliation(s)
- Chao-Hung Kuo
- Division of Internal Medicine, Kaohsiung Municipal Hsiao-Kang Hospital, Kaohsiung, Taiwan
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In vitro susceptibility to antimicrobial agents and ultrastructural characteristics related to swimming motility and drug action in Campylobacter jejuni and C. coli. J Infect Chemother 2010; 16:174-85. [PMID: 20225076 DOI: 10.1007/s10156-010-0040-1] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/30/2009] [Accepted: 01/20/2010] [Indexed: 10/19/2022]
Abstract
Campylobacter jejuni has recently been noted as the most common cause of bacterial food-borne diseases in Japan. In this study, we examined in vitro susceptibility to 36 antimicrobial agents of 109 strains of C. jejuni and C. coli isolated from chickens and patients with enteritis or Guillain-Barré syndrome from 1996 to 2009. Among these agents, carbapenems (imipenem, meropenem, panipenem, and biapenem) showed the greatest activity [minimal inhibitory concentration (MIC)(90), 0.03-0.125 microg/ml]. This was followed by sitafloxacin (MIC(90), 0.25 microg/ml), furazolidone and azithromycin (MIC(90), 0.5 microg/ml), gentamicin and clindamycin (MIC(90), 1 microg/ml), and clavulanic acid (beta-lactamase inhibitor; MIC(90), 2 microg/ml). All or most strains were resistant to aztreonam, sulfamethoxazole, and trimethoprim. Marked resistance was also observed for levofloxacin and tetracyclines. Resistance was not present for macrolides and rare for clindamycin. C. jejuni (and C. coli) exhibited high swimming motility and possessed a unique end-side (cup-like) structure at both ends, in contrast to Helicobacter pylori and Vibrio cholerae O1 and O139. The morphology of C. jejuni (and C. coli) changed drastically after exposure to imipenem (coccoid formation), meropenem (bulking and slight elongation), and sitafloxacin (marked elongation), and exhibited reduced motility. In the HEp-2 cell adherence model, unusually elongated bacteria were also observed for sitafloxacin. The data suggest that although resistance to antimicrobial agents (e.g., levofloxacin) has continuously been noted, carbapenems, sitafloxacin, and others such as beta-lactamase inhibitors alone showed good in vitro activity and that C. jejuni (and C. coli) demonstrated a unique ultrastructural nature related to high swimming motility and drug action.
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Yang JC, Lin CJ. CYP2C19 genotypes in the pharmacokinetics/pharmacodynamics of proton pump inhibitor-based therapy of Helicobacter pylori infection. Expert Opin Drug Metab Toxicol 2010; 6:29-41. [PMID: 19968574 DOI: 10.1517/17425250903386251] [Citation(s) in RCA: 41] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
IMPORTANCE OF THE FIELD Proton pump inhibitors (PPIs) are potent gastric acid inhibitors. Therapies with a PPI and antibiotics are used to cure Helicobacter pylori (H. pylori) infection, which is closely related to many gastrointestinal diseases. Most PPIs are mainly metabolized by cytochrome 2C19 (CYP2C19). The genetic polymorphisms of CYP2C19 may lead to the differences in pharmacokinetics (PK), pharmacodynamics (PD) and clinical efficacy of PPIs. AREAS COVERED IN THIS REVIEW The roles of PPIs on the eradication of H. pylori are summarized. The impact f CYP2C19 polymorphism on the PK and PD of PPIs is addressed and related to the present status of therapy for H. pylori infection. The opinions on the strategy of PPIs-based therapies of H. pylori infection are provided. WHAT THE READER WILL GAIN Update the factors that may influence the PPIs-based therapies of H. pylori infection. TAKE HOME MESSAGE The eradication rates of H. pylori infection are significantly different between patients who are CYP2C19 extensive metabolizers and poor metabolizers, partly because of the differences in the PK and PD of PPIs. Nonetheless, the differences can be improved by adjusting the regimens of PPIs and using antibiotics that have less H. pylori-resistance.
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Affiliation(s)
- Jyh-Chin Yang
- National Taiwan University, Hospital and College of Medicine, Department of Internal Medicine, Taipei, Taiwan
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Yang JC, Yang YF, Uang YS, Lin CJ, Wang TH. Pharmacokinetic- pharmacodynamic analysis of the role of CYP2C19 genotypes in short-term rabeprazole-based triple therapy against Helicobacter pylori. Br J Clin Pharmacol 2009; 67:503-10. [PMID: 19552744 DOI: 10.1111/j.1365-2125.2009.03393.x] [Citation(s) in RCA: 12] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022] Open
Abstract
AIMS The aim was to explore the role of CYP2C19 polymorphism in short-term rabeprazole-based triple therapy against Helicobacter pylori infection. METHODS Patients with H. pylori infection were tested for CYP2C19 genotype as poor metabolizers (PMs) or extensive metabolizers (EMs, homozygous EM or heterozygous EM) and given rabeprazole for 7 days. Antibiotics (clarithromycin and amoxicillin) were given on days 1-4, days 4-7, or days 1-7. A direct link model with an effect compartment was used in the population pharmacokinetic-pharmacodynamic analysis. The status of H. pylori infection was evaluated. RESULTS Rabeprazole clearance was lower in CYP2C19 PMs than in EMs (with average values of 10.7 vs. 16.8 l h(-1) in PMs and EMs, respectively), resulting in higher plasma levels in the former group. The values of EC(50) and k(eo) of gastrin response increased with multiple doses of rabeprazole. The k(eo) values were lower in CYP2C19 PMs than in EMs on day 1 (0.012 vs. 0.017 x 10(-4) l min(-1)), and higher than in EMs on day 4 (0.804 vs. 0.169 x 10(-4) l min(-1)) of rabeprazole treatment. The predicted gastrin-time profile showed a higher response in CYP2C19 PMs than in EMs on days 4 and 7. Helicobacter pylori was eradicated in all CYP2C19 PMs except in one patient infected by a resistant strain. In contrast, in CYP2C19 EMs the eradication rates ranged from 58 to 85%. CONCLUSIONS CYP2C19 genotypes play a role in H. pylori eradication therapy. Rabeprazole-based short-term triple therapy may be applicable in CYP2C19 PMs for H. pylori eradication.
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Affiliation(s)
- Jyh-Chin Yang
- Department of Internal Medicine, Hospital and College of Medicine, National Taiwan University, Taipei, Taiwan
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Ogura K, Mitsuno Y, Maeda S, Hirata Y, Yanai A, Shibata W, Ohmae T, Yoshida H, Kawabe T, Omata M. Efficacy and safety of faropenem in eradication therapy of Helicobacter pylori. Helicobacter 2007; 12:618-22. [PMID: 18001403 DOI: 10.1111/j.1523-5378.2007.00551.x] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/09/2022]
Abstract
AIMS While triple therapy with a proton pump inhibitor, amoxicillin, and clarithromycin is the standard therapy for Helicobacter pylori eradication, it is ineffective against clarithromycin-resistant strains. To seek a better regimen for eradication therapy, we assessed the sensitivity of clinical strains seen in Japan to faropenem and then evaluated the efficacy and safety of eradication therapy containing this antibiotic. METHODS Minimum inhibitory concentrations (MICs) of faropenem were determined in 78 Japanese clinical H. pylori isolates using the agar dilution method. H. pylori-positive patients were consecutively assigned to a 7-day eradication therapy protocol with LAF (lansoprazole 60 mg/day, amoxicillin 2000 mg/day, and faropenem 600 mg/day), and then to a 14-day protocol. The outcomes of the therapies were assessed by (13)C-urea breath tests. RESULTS All 78 strains showed MICs of faropenem that were equal to or less than 0.2 microg/mL. The eradication rates according to intention-to-treat analyses were 46.5% with the 7-day therapy (n = 43) and 62.5% with the 14-day therapy (n = 32). No special measures were required to treat the adverse events observed in approximately one-third of the patients. CONCLUSIONS Faropenem was found to have good antimicrobial action against H. pylori in vitro. The 14-day LAF therapy successfully eradicated H. pylori in about two-thirds of the patients although the incidence of adverse events was high.
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Affiliation(s)
- Keiji Ogura
- Department of Gastroenterology, Graduate School of Medicine, University of Tokyo, 7-3-1 Hongo, Tokyo 113-8655, Japan.
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22
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Takeda K, Utsunomiya H, Kakiuchi S, Okuno Y, Oda K, Inada KI, Tsutsumi Y, Tanaka T, Kakudo K. Citrus Auraptene Reduces Helicobacter pylori Colonization of Glandular Stomach Lesions in Mongolian Gerbils. J Oleo Sci 2007; 56:253-60. [PMID: 17898489 DOI: 10.5650/jos.56.253] [Citation(s) in RCA: 22] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022] Open
Abstract
We examined the efficacy of auraptene (AUR), an antioxidant agent of a citrus coumarin derivative, for suppressing gastric inflammation introduced by Helicobacter pylori (Hp) infection in Mongolian gerbils (MGs). Hp-infected MGs were placed on diets containing 100 or 500 ppm AUR for 7 weeks. Real-time PCR was used to estimate the Hp population in glandular stomach lesions, and a histological assessment of inflammation was performed. At a dose of 500 ppm, AUR reduced the Hp population to 21.9+/-12.0% of the control group (p<0.05). However, no apparent differences were seen in hematoxylin and eosin sections between AUR-administered and control groups. We conclude that dietary supplementation with 500 ppm of AUR suppresses Hp colonization, but does not reduce gastric inflammation.
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Affiliation(s)
- Koichi Takeda
- Second Department of Pathology, Wakayama Medical University, Kimiidera, Wakayama, Japan
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Miyazawa M, Utsunomiya H, Inada KI, Yamada T, Okuno Y, Tanaka H, Tatematsu M. Inhibition of Helicobacter pylori motility by (+)-Syringaresinol from unripe Japanese apricot. Biol Pharm Bull 2006; 29:172-3. [PMID: 16394533 DOI: 10.1248/bpb.29.172] [Citation(s) in RCA: 39] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022]
Abstract
A methanol extract from unripe Japanese apricot showed inhibitory activity of Helicobacter pylori motility. Inhibitory compound 1 was isolated and identified as (+)-syringaresinol (1) by spectoroscopic means. (+)-Syringaresinol (1) inhibited >90% of the H. pylori motility at a concentration of 500 microg/ml and the IC50 value was 50 microg/ml.
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Affiliation(s)
- Mitsuo Miyazawa
- Department of Applied Chemistry, Faculty of Science and Engineering, Kinki University.
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24
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Giannini EG, Bilardi C, Dulbecco P, Mamone M, Santi ML, Testa R, Mansi C, Savarino V. A study of 4- and 7-day triple therapy with rabeprazole, high-dose levofloxacin and tinidazole rescue treatment for Helicobacter pylori eradication. Aliment Pharmacol Ther 2006; 23:281-7. [PMID: 16393308 DOI: 10.1111/j.1365-2036.2006.02756.x] [Citation(s) in RCA: 12] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
BACKGROUND Helicobacter pylori treatment failure is becoming an emergent problem in clinical practice. Shorter treatment duration should improve compliance to therapy and keep an acceptable H. pylori eradication rate. AIMS To evaluate the efficacy of two rabeprazole, high-dose levofloxacin and tinidazole-based regimens as 'rescue' treatment for H. pylori eradication in an open-label, randomized, pilot study carried out in a clinical practice setting. METHODS Eighty-five consecutive patients who have previously failed at least one H. pylori eradication attempt were randomized to receive rabeprazole (20 mg, b.d.), levofloxacin (500 mg, b.d.) and tinidazole (500 mg, b.d.) either for 4 (4-day RLT, n = 42) or 7 days (7-day RLT, n = 43). Cure of H. pylori infection was assessed by means of 13C-urea breath test. RESULTS The 7-day RLT achieved 84% (95% CI: 69-93%) and 86% (95% CI: 72-95%) eradication rates in intention-to-treat and per-protocol analyses respectively. The shorter treatment obtained an 83% (95% CI: 69-93%) eradication rate in both intention-to-treat and per-protocol analysis. Both regimens were well tolerated, although patients who received the 4-day RLT reported fewer side-effects. CONCLUSIONS In patients who have previously failed at least one H. pylori eradication attempt, both 4- and 7-day rabeprazole, high-dose levofloxacin, tinidazole-based regimens are effective in curing the infection in more than 80% of patients.
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Affiliation(s)
- E G Giannini
- Gastroenterology Unit, Department of Internal Medicine, University of Genoa, Genoa, Italy.
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25
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Wong WM, Huang J, Xia HHX, Fung FMY, Tong TSM, Cheung KL, Ho VYK, Lai KC, Chan CK, Chan AOO, Hui CK, Lam SK, Wong BCY. Low-dose rabeprazole, amoxicillin and metronidazole triple therapy for the treatment of Helicobacter pylori infection in Chinese patients. J Gastroenterol Hepatol 2005; 20:935-940. [PMID: 15946144 DOI: 10.1111/j.1440-1746.2005.03889.x] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/05/2023]
Abstract
BACKGROUND Rabeprazole in combination with amoxicillin and metronidazole (RAM) has been shown to be an effective second-line treatment of Helicobacter pylori infection. The effects were compared of 7-day low-dose and high dose rabeprazole in RAM for the primary treatment of H. pylori infection in Chinese patients. METHODS Helicobacter pylori-positive dyspeptic patients were randomized to receive either (i) rabeprazole 10 mg, amoxicillin 1000 mg and metronidazole 400 mg (RAM-10) or (ii) high-dose rabeprazole 20 mg, amoxicillin 1000 mg and metronidazole 400 mg (RAM-20), each given twice daily for 7 days. Helicobacter pylori eradication was confirmed by (13)c-urea breath test 5 weeks after stopping medications. side-effects of treatments were documented. RESULTS A total of 120 patients were eligible for analysis. By intention-to-treat and per-protocol analysis, the eradication rates were 83% and 86% in the RAM-10 group and 75% and 76% in the RAM-20 group, respectively (P = 0.26 and P = 0.17). Both regimens were well-tolerated and compliance was >98% in both groups. CONCLUSIONS Low-dose rabeprazole in combination with amoxicillin and metronidazole is an effective, economical and well-tolerated therapy for the treatment of H. pylori infection in Chinese population.
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Affiliation(s)
- Wai Man Wong
- Department of Medicine, Queen Mary Hospital, University of Hong Kong, Pokfulam Road, Hong Kong
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Wang HH, Chou JW, Liao KF, Lin ZY, Lai HC, Hsu CH, Chen CB. One-year follow-up study of Helicobacter pylori eradication rate with 13C-urea breath test after 3-d and 7-d rabeprazole-based triple therapy. World J Gastroenterol 2005; 11:1680-4. [PMID: 15786549 PMCID: PMC4305953 DOI: 10.3748/wjg.v11.i11.1680] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
AIM: To investigate the long-term role of a 3-d rabeprazole-based triple therapy in patients with Helicobacter pylori(H pylori)-infected active peptic ulcers.
METHODS: We prospectively studied 115 consecutive patients with H pylori-infected active peptic ulcers. H pylori infection was confirmed if any two of H pylori DNA, histology, and rapid urease test were positive. Patients were assigned to either an open-labeled 3-d course of oral amoxicillin 1000 mg b.i.d., clarithromycin 500 mg b.i.d., and rabeprazole 20 mg b.i.d., or 7-d course of oral amoxicillin 1000 mg b.i.d., clarithromycin 500 mg b.i.d., and rabeprazole 20 mg b.i.d. Subsequently, all patients received oral rabeprazole 20 mg once daily until the 8th wk. Three months after therapy, all patients were followed-up endoscopically for the peptic ulcer, H pylori DNA, histology, and rapid urease test. One year after therapy, H pylori infection was tested using the 13C-urea breath test.
RESULTS: The ulcer healing rates 3 mo after therapy were 81.0% vs 75.4% for the 3-d and 7-d groups [intention-to-treat (ITT) analysis, P = 0.47] respectively, and 90.4% vs 89.6% for the 3-d and 7-d groups [per-protocol (PP) analysis, P = 0.89] respectively. The eradication rates 3 mo after therapy were 75.9% vs 73.7% for the 3-d and 7-d groups (ITT, P = 0.79) respectively, and 84.6% vs 87.5% for the 3-d and 7-d groups (PP, P = 0.68) respectively. One year after therapy, seventy-five patients returned to receive the 13C-urea breath test, and the eradication rates were 78.4% vs 81.6% in 3-d and 7-d groups (PP, P = 0.73) respectively.
CONCLUSION: Our study showed the eradication rates against H pylori infection 3 and 12 mo after triple therapy were not different between the 3-d and 7-d rabeprazole-based groups. Therefore, the 3-d rabeprazole-based triple therapy may be an alternative treatment for peptic ulcers with H pylori infection.
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Affiliation(s)
- Hwang-Huei Wang
- Division of Gastroenterology, Department of Internal Medicine, China Medical University Hospital, 2 Yuh-Der Road, North District, Taichung 404, Taiwan, China.
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Spengler G, Molnar A, Klausz G, Mandi Y, Kawase M, Motohashi N, Molnar J. Inhibitory action of a new proton pump inhibitor, trifluoromethyl ketone derivative, against the motility of clarithromycin-susceptible and-resistant Helicobacter pylori. Int J Antimicrob Agents 2005; 23:631-3. [PMID: 15194136 DOI: 10.1016/j.ijantimicag.2003.11.010] [Citation(s) in RCA: 22] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/24/2003] [Accepted: 11/28/2003] [Indexed: 12/13/2022]
Abstract
We previously reported that a trifluoromethyl ketone derivative, 1-(2-benzoxazolyl)-3,3,3-trifluoro-2-propanone (TF18), exhibited the potent antibacterial activity against Helicobacter pylori, but had no urease activity. In order to clarify the mechanism of anti-H. pylori action of TF18, we evaluated the growth and motility of TF18 on clarithromycin-susceptible H. pylori (CSHP) and -resistant H. pylori (CRHP). An effective proton pump inhibitor (TF18) had remarkable dose-dependent antibacterial activity and was able to inhibit the flagellar motor of both CSHP and CRHP isolates. The antimotility effect of TF18 was more pronounced at subinhibitory concentration in CRHP than in CSHP. The swimming (the forward motion) was more sensitive to the inhibition than the tumbling. Based on the results, it is supposed that TF18 works as an uncoupler similar to the 'clutch' in a biological motor, in which counterclockwise rotation is more sensitive to the effect of TF18 than the clockwise rotation.
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Affiliation(s)
- Gabriella Spengler
- Department of Medical Microbiology and Immunobiology, Albert Szent-Györgyi Medical Centre, Faculty of Medicine, University of Szeged, Szeged, Hungary
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Abstract
At present, antisecretory drugs--foremost among them the proton pump inhibitors (PPIs)--represent a keystone in Helicobacter pylori eradication therapy. The present article shall first compare the role of PPIs as compared with histamine H2 receptor antagonists, both of them in the role of antibiotic-associated antisecretory therapy, and shall then address the contribution of each of the various PPIs that have been developed until the present time to the H. pylori eradication therapies. In summary, it may be concluded that PPIs are more effective overall than H2 receptor antagonists when the two groups of antisecretory drugs are given at the usual standard doses together with antibiotics with the intention of eradicating H. pylori infection. However, all PPIs (omeprazole, lansoprazole, pantoprazole, rabeprazole, and esomeprazole) are equivalent when given together with two antibiotics to cure the infection.
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Affiliation(s)
- Javier P Gisbert
- Gastroenterology Service, La Princesa University Hospital, Madrid, Spain.
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Joseph IM, Kirschner D. A model for the study of Helicobacter pylori interaction with human gastric acid secretion. J Theor Biol 2004; 228:55-80. [PMID: 15064083 DOI: 10.1016/j.jtbi.2003.12.004] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/12/2003] [Revised: 12/05/2003] [Accepted: 12/08/2003] [Indexed: 12/21/2022]
Abstract
We present a comprehensive mathematical model describing Helicobacter pylori interaction with the human gastric acid secretion system. We use the model to explore host and bacterial conditions that allow persistent infection to develop and be maintained. Our results show that upon colonization, there is a transient period (day 1-20 post-infection) prior to the establishment of persistence. During this period, changes to host gastric physiology occur including elevations in positive effectors of acid secretion (such as gastrin and histamine). This is promoted by reduced somatostatin levels, an inhibitor of acid release. We suggest that these changes comprise compensatory mechanisms aimed at restoring acid to pre-infection levels. We also show that ammonia produced by bacteria sufficiently buffers acid promoting bacteria survival and growth.
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Affiliation(s)
- Ian M Joseph
- Department of Microbiology and Immunology, The University of Michigan Medical School, 6730 Medical Science Building II, Ann Arbor, MI 48109-0620, USA
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Schreiber S, Konradt M, Groll C, Scheid P, Hanauer G, Werling HO, Josenhans C, Suerbaum S. The spatial orientation of Helicobacter pylori in the gastric mucus. Proc Natl Acad Sci U S A 2004; 101:5024-9. [PMID: 15044704 PMCID: PMC387367 DOI: 10.1073/pnas.0308386101] [Citation(s) in RCA: 241] [Impact Index Per Article: 11.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022] Open
Abstract
The highly motile human pathogen Helicobacter pylori lives deep in the gastric mucus layer. To identify which chemical gradient guides the bacteria within the mucus layer, combinations of luminal perfusion, dialysis, and ventilation were used to modify or invert transmucus gradients in anaesthetized Helicobacter-infected mice and Mongolian gerbils. Neither changes in lumen or arterial pH nor inversion of bicarbonate/CO2 or urea/ammonium gradients disturbed Helicobacter orientation. However, elimination of the mucus pH gradient by simultaneous reduction of arterial pH and bicarbonate concentration perturbed orientation, causing the bacteria to spread over the entire mucus layer. H. pylori thus uses the gastric mucus pH gradient for chemotactic orientation.
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Affiliation(s)
- Sören Schreiber
- Institut für Physiologie, Ruhr-Universität Bochum, D-44780 Bochum, Germany.
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Wolfart K, Molnar A, Kawase M, Motohashi N, Molnar J. Effects of Trifluoromethyl Ketones on the Motility of Proteus vulgaris. Biol Pharm Bull 2004; 27:1462-4. [PMID: 15340240 DOI: 10.1248/bpb.27.1462] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022]
Abstract
In the present study, we showed the inhibition of motility by trifluoromethyl ketone (TF) derivatives (1-8) in Proteus vulgaris (P. vulgaris) cultures. Among them, 1-(2-benzoxazoyl)-3,3,3-trifluoro-2-propanone (1) showed a much stronger inhibitory effect on the motility of P. vulgaris than other TF compounds at 10% MIC. Our results suggest the possibility of an inhibitory action of TF compounds on the proton motive forces by affecting the action of biological motor and proton efflux in the membranes, resulting in a reduction of the ratio of running and the increased number of tumbling and non-motile cells.
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Affiliation(s)
- Krisztina Wolfart
- Department of Medical Microbiology, Faculty of General Medicine, University of Szeged, Szeged, H-6720, Hungary
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Gambaro C, Bilardi C, Dulbecco P, Iiritano E, Zentilin P, Mansia C, Usai P, Vigneri S, Savarino V. Comparable Helicobacter pylori eradication rates obtained with 4- and 7-day rabeprazole-based triple therapy: a preliminary study. Dig Liver Dis 2003; 35:763-7. [PMID: 14674665 DOI: 10.1016/s1590-8658(03)00458-4] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
BACKGROUND Rabeprazole is a new proton pump inhibitor, which has been reported to induce a faster acid suppression than other drugs of the same category. This might be useful to reduce the duration of anti-Helicobacter therapies. AIMS The aim of this study was to assess whether there is the possibility of shortening a rabeprazole-based triple therapy from 7 to 4 days without compromising its efficacy in the eradication of Helicobacter pylori infection. PATIENTS A total of 128 consecutive dyspeptic patients with H. pylori infection were recruited for this controlled, randomized, open and parallel-group trial comparing the efficacy of two durations of the same rabeprazole-based triple therapy. METHODS All patients were subdivided to receive a combination of rabeprazole 20 mg twice daily, clarithromycin 250 mg twice daily and metronidazole 500 mg twice daily (RCM) for 4 days (n = 63) and for 7 days (n = 65). At baseline, they underwent breath 13C-urea test and endoscopy with biopsies for rapid urease testing and histology to confirm infection with H. pylori. Eradication was determined by a negative 13C-urea breath test within 28-32 days after the end of therapy. RESULTS Overall eradication rates were similar for patients treated with the 4- and the 7-day periods (intention-to-treat and per-protocol analyses showed a success rate of 81% versus 78% and 88% versus 85%, respectively; P = NS). Tolerance was similar in both groups. Most adverse events were mild to moderate, and only two patients were withdrawn because of them. CONCLUSIONS The eradication rate of the 4-day regimen was equivalent to that of the same 7-day regimen based on rabeprazole plus clarithromycin and metronidazole. Therefore, the 4-day regimen of RCM seems to give us the possibility of adopting a shorter-than-usual duration of therapy against H. pylori.
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Affiliation(s)
- C Gambaro
- Department of Internal Medicine, University of Genoa, Viale Benedetto XV, n. 6, Genoa 16132, Italy
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Suzuki H, Miyazawa M, Nagahashi S, Sato M, Bessho M, Nagata H, Miura S, Ishii H. Rabeprazole treatment attenuated Helicobacter pylori-associated gastric mucosal lesion formation in Mongolian gerbils. J Gastroenterol Hepatol 2003; 18:787-95. [PMID: 12795750 DOI: 10.1046/j.1440-1746.2003.03038.x] [Citation(s) in RCA: 13] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/09/2022]
Abstract
BACKGROUND AND AIM Although rabeprazole (RPZ), a proton pump inhibitor, has been reported to have a bactericidal effect on Helicobacter pylori (H. pylori), no studies have been conducted regarding the effect of RPZ on gastric mucosal lesion formation caused by this bacterium. In the present study, we investigated the effect of RPZ on H. pylori-associated gastric mucosal lesion formation. METHODS Sixty-two male Mongolian gerbils were inoculated with H. pylori (ATCC43504) (Hp group) and 60 gerbils with the culture media alone (control group). Some gerbils in the Hp group and in the control group were injected with RPZ (1 mg/kg/day, for 7 days) at the 5th week. Gerbils were evaluated at the 12th, 24th and 48th weeks. RESULTS In the Hp group, all gerbils were persistently infected for 24 weeks, but 36% became negative for H. pylori at the 48th week. In the Hp + RPZ group, 18% of gerbils at the 12th week, 40% at the 24th week, and 80% at the 48th week, became negative for H. pylori. The level of neutrophil infiltration was significantly decreased in the Hp + RPZ group in comparison to the Hp group, possibly through the effects of RPZ on initial bacterial colonization and resultant inflammation. Even in the gerbils that became H. pylori-negative, the level of neutrophil infiltration was lower in the Hp + RPZ group than in the Hp group. RPZ treatment significantly increased the level of the reduced form of glutathione (GSH) at the 48th week. The elevated levels of the reduced form of GSH may have been reduced by an antioxidation process in the H. pylori-positive Hp + RPZ group. CONCLUSION Administration of RPZ not only inhibited gastric H. pylori colonization, but also reduced gastric mucosal inflammation in gerbils, possibly through its antibacterial action as well as pharmacological recruitment of the reduced form of GSH.
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Affiliation(s)
- Hidekazu Suzuki
- Department of Internal Medicine, School of Medicine, Keio University, Tokyo, Japan.
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Lin CJ, Yang JC, Uang YS, Chern HD, Wang TH. Time-dependent amplified pharmacokinetic and pharmacodynamic responses of rabeprazole in cytochrome P450 2C19 poor metabolizers. Pharmacotherapy 2003; 23:711-9. [PMID: 12820812 DOI: 10.1592/phco.23.6.711.32177] [Citation(s) in RCA: 16] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/11/2023]
Abstract
STUDY OBJECTIVES To determine the pharmacokinetic and pharmacodynamic rationale for the optimum regimen of rabeprazole in the treatment of Helicobacter pylori infection in patients who are cytochrome P450 (CYP) 2C19 poor metabolizers or extensive metabolizers. DESIGN Prospective, multiple-dose pharmacokinetic and pharmacodynamic study. SETTING University-affiliated medical center in Taiwan. SUBJECTS Twelve healthy volunteers (aged 20-30 yrs) who were identified as CYP2C19 poor metabolizers (six subjects) or extensive metabolizers (six). INTERVENTION Each subject received rabeprazole 20 mg twice/day for 3 consecutive days and once/day on the fourth day. MEASUREMENTS AND MAIN RESULTS Pharmacokinetic and pharmacodynamic parameters were compared between CYP2C19 poor and extensive metabolizers on day 1 and day 4 of dosing. The mean +/- SD values of area under the concentration-time curve of rabeprazole and rabeprazole thioether were significantly higher in poor metabolizers than in extensive metabolizers on day 1 (5357 +/- 883 vs 1131 +/- 512 ng x hr/ml and 1703 +/- 432 vs 561 +/- 358 ng x hr/ml, respectively; p<0.001) and on day 4 (5601 +/- 669 vs 1619 +/- 778 ng x hr/ml and 1914 +/- 378 vs 511 +/- 360 ng x hr/ml, respectively; p<0.001). However, no significant difference was noted between day 1 and day 4 of dosing within the same genotype groups. Only CYP2C19 poor metabolizers had significantly higher plasma gastrin levels on day 4 compared with those levels on day 1 (p<0.05). The pharmacokinetic-pharmacodynamic relationship of rabeprazole appears to be time dependent. CONCLUSION The pharmacokinetic and pharmacodynamic data suggest that CYP2C19 poor metabolizers might be subject to advantageous conditions, especially after day 4, for treating H. pylori infection with rabeprazole.
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Affiliation(s)
- Chun-Jung Lin
- Graduate Institute of Clinical Pharmacy, College of Medicine, National Taiwan University, Taipei
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Gisbert JP, Khorrami S, Calvet X, Pajares JM. Systematic review: Rabeprazole-based therapies in Helicobacter pylori eradication. Aliment Pharmacol Ther 2003; 17:751-64. [PMID: 12641497 DOI: 10.1046/j.1365-2036.2003.01450.x] [Citation(s) in RCA: 23] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
AIM To perform a systematic review of the efficacy of rabeprazole-based therapies in Helicobacter pylori eradication, and to conduct a meta-analysis comparing the efficacy of rabeprazole and other proton pump inhibitors when co-prescribed with antibiotics. METHODS Studies evaluating rabeprazole plus antibiotics were considered. Only randomized trials comparing rabeprazole and other proton pump inhibitors with antibiotics, and differing only in the proton pump inhibitor, were included in the meta-analysis. Electronic and manual bibliographic searches were conducted. The percentage (weighted mean) of successful eradication was calculated. Meta-analysis was performed by combining the odds ratios (OR) of the individual studies. RESULTS The eradication rates were as follows: 14-day rabeprazole-amoxicillin, 73%; rabeprazole-amoxicillin-clarithromycin for 3, 5, 7 and 10 days, 44%, 72%, 78% and 75%, respectively; low-dose rabeprazole (20 mg/day), amoxicillin and clarithromycin for 7 days, 81%; high-dose rabeprazole (40 mg/day), amoxicillin and clarithromycin for 7 days, 75%; 7-day rabeprazole-clarithromycin-nitroimidazole, 85%. Twelve comparative studies were included in the meta-analysis. The eradication rate with rabeprazole plus antibiotics was 79%; it was 77% with other proton pump inhibitors (OR = 1.15; 95% confidence interval, 0.93-1.42). Sub-analysis comparing rabeprazole at low doses (10 mg b.d.) with other proton pump inhibitors at standard doses (omeprazole 20 mg b.d. or lansoprazole 30 mg b.d.) showed no differences. CONCLUSIONS Rabeprazole achieves similar H. pylori eradication rates to omeprazole and lansoprazole when co-prescribed with antibiotics. Low doses of rabeprazole (10 mg b.d.), when administered with two antibiotics, may be sufficient to eradicate H. pylori infection.
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Affiliation(s)
- J P Gisbert
- Servicio de Aparato Digestivo, Hospital Universitario de la Princesa, Madrid, Spain.
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Wong WM, Gu Q, Lam SK, Fung FMY, Lai KC, Hu WHC, Yee YK, Chan CK, Xia HHX, Yuen MF, Wong BCY. Randomized controlled study of rabeprazole, levofloxacin and rifabutin triple therapy vs. quadruple therapy as second-line treatment for Helicobacter pylori infection. Aliment Pharmacol Ther 2003; 17:553-560. [PMID: 12622764 DOI: 10.1046/j.1365-2036.2003.01459.x] [Citation(s) in RCA: 92] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
AIM To test the efficacy of rabeprazole, levofloxacin and rifabutin triple therapy vs. quadruple therapy for the second-line treatment of Helicobacter pylori infection. METHODS One hundred and nine patients who had failed previous H. pylori eradication were randomized to receive: (i) rabeprazole, 20 mg b.d., rifabutin, 300 mg once daily, and levofloxacin, 500 mg once daily, for 7 days (triple therapy); or (ii) rabeprazole, 20 mg b.d., metronidazole, 400 mg t.d.s., bismuth subcitrate, 120 mg q.d.s., and tetracycline, 500 mg q.d.s., for 7 days (quadruple therapy). Endoscopy and culture were performed before treatment. RESULTS The clarithromycin (79% vs. 21%, P < 0.001) and metronidazole (89% vs. 40%, P < 0.001) resistance rates were significantly higher in patients with previous exposure than in those with no previous exposure. The intention-to-treat and per protocol eradication rates were 91%/91% for the triple therapy group and 91%/92% for the quadruple therapy group. For patients with double resistance to metronidazole and clarithromycin, the eradication rates were 85% (17/20) in the triple therapy group and 87% (13/15) in the quadruple therapy group. Compliance was greater than 95% for both regimens. CONCLUSION Rabeprazole, levofloxacin and rifabutin-based triple therapy and quadruple therapy were equally effective as second-line treatments for H. pylori infection.
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Affiliation(s)
- W M Wong
- Department of Medicine, University of Hong Kong, Queen Mary Hospital, Hong Kong, China
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Thjodleifsson B, Rindi G, Fiocca R, Humphries TJ, Morocutti A, Miller N, Bardhan KD. A randomized, double-blind trial of the efficacy and safety of 10 or 20 mg rabeprazole compared with 20 mg omeprazole in the maintenance of gastro-oesophageal reflux disease over 5 years. Aliment Pharmacol Ther 2003; 17:343-51. [PMID: 12562446 DOI: 10.1046/j.1365-2036.2003.01446.x] [Citation(s) in RCA: 44] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
BACKGROUND Gastro-oesophageal reflux disease has a chronic course, and often requires long-term treatment. Proton pump inhibitors are the treatment of choice for both acute and maintenance treatment, but little is known from randomized controlled trials of their effects beyond 1 year. AIM To compare the efficacy and safety of two doses of rabeprazole with 20 mg omeprazole in the maintenance treatment of erosive gastro-oesophageal reflux disease over 5 years. METHODS Two hundred and forty-three patients who had previously responded to acute treatment for erosive gastro-oesophageal reflux disease were prospectively randomized to receive 5 years of treatment with rabeprazole (10 or 20 mg daily) or omeprazole (20 mg daily). The primary outcome measure was endoscopically confirmed relapse of erosive gastro-oesophageal reflux disease. RESULTS One hundred and twenty-three patients (51%) completed all 5 years of the study, with similar completion rates in the three groups. Relapses occurred in nine of 78 (11.5%), eight of 82 (9.8%) and 11 of 83 (13.3%) patients in the rabeprazole 20 mg, rabeprazole 10 mg and omeprazole 20 mg groups, respectively. Gastric biopsy showed no evidence of any harmful effects. All treatments were well tolerated. CONCLUSIONS Rabeprazole 10 mg, rabeprazole 20 mg and omeprazole 20 mg all had similar efficacy in the maintenance treatment of gastro-oesophageal reflux disease. All three were safe and well tolerated during 5 years of treatment.
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Abstract
Rabeprazole's favourable pharmacodynamic profile is a result of its rapid onset and its 24-h control of gastric parietal secretion. These qualities, and its antimicrobial properties, make it particularly effective in the treatment of Helicobacter pylori (H. pylori), which is a short course of treatment compared to other conditions treated with proton pump inhibitors. Recently completed trials in combination with amoxicillin, clarithromycin and metronidazole for 7 days achieved high eradication of H. pylori. An additional study assessing the efficacy of combined rabeprazole and antibiotic treatments of 3, 7, and 10 days' duration vs. FDA-approved 10-day omeprazole triple therapy is under way to address the possibility of shorter duration therapies in the USA.
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Affiliation(s)
- J Barth
- Clinical Research & Development, Eisai Inc., Teaneck, NJ 07666, USA.
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Abstract
Many bacteria that cause diseases of humans, animals and plants use flagella to move. This review summarises recent studies that have analysed the role of motility and chemotaxis in the host-parasite relationship of pathogenic bacteria. These studies have shown that for many pathogens, motility is essential in some phases of their life cycle and that virulence and motility are often intimately linked by complex regulatory networks. Possibilities to exploit bacterial motility as a specific therapeutic antibacterial target to cure or prevent disease are discussed.
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Abstract
UNLABELLED Rabeprazole is an inhibitor of the gastric proton pump. It causes dose-dependent inhibition of acid secretion. In 8-week studies, among patients with gastro-oesophageal reflux disease (GORD), rabeprazole 20 mg/day or 10mg twice daily was as effective as omeprazole and superior to ranitidine in the healing of GORD. Symptom relief with rabeprazole was superior to that provided by placebo and ranitidine and similar to omeprazole. In long-term trials rabeprazole 10 mg/day was similar to omeprazole 20 mg/day in a 2-year study and superior to placebo in 1-year studies, in both the maintenance of healing and prevention of symptoms in patients with healed GORD. In nonerosive GORD, 4-week studies have shown rabeprazole to be more effective than placebo in relieving heartburn and various other gastrointestinal symptoms. Data among patients with Barrett's oesophagus suggest rabeprazole 20 mg/day may be more effective than placebo in maintaining healing of associated oesophagitis after 1 year of treatment. One-week triple Helicobacter pylori eradication therapy with rabeprazole plus clarithromycin and amoxicillin achieved eradication rates of > or =85%. Rabeprazole is as effective as omeprazole and lansoprazole when included as part of a triple-therapy regimen for the eradication of H. pylori. Eradication rates of >90% were achieved when rabeprazole 20 to 40 mg/day was included as part of a quadruple eradication regimen. As monotherapy for peptic ulcer healing and symptom relief, 4- to 8-week studies have shown rabeprazole 10 to 40 mg/day to be superior to placebo and ranitidine and have similar efficacy to omeprazole. Preliminary 1-year data among 16 patients with Zollinger-Ellison syndrome suggest rabeprazole 60 to 120 mg/day can resolve and prevent the recurrence of symptoms and endoscopic lesions associated with this condition. In clinical trials of up to 2 years' duration the tolerability of rabeprazole is similar to that of placebo, ranitidine and omeprazole. Common adverse events assigned to rabeprazole have been diarrhoea, headache, rhinitis, nausea, pharyngitis and abdominal pain. Histological changes and increases in serum gastrin levels were unremarkable and typical of proton pump inhibitors. No dosage adjustment is necessary in renal and mild to moderate hepatic impairment. CONCLUSION Rabeprazole is a well tolerated proton pump inhibitor. It has proven efficacy in healing, symptom relief and prevention of relapse of peptic ulcers and GORD and can form part of effective H. pylori eradication regimens. It is an important alternative to H(2) antagonists and an additional treatment option to other proton pump inhibitors in the management of acid-related disorders.
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Affiliation(s)
- C I Carswell
- Adis International Limited, Auckland, New Zealand.
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Wong BC, Wong WM, Yee YK, Hung WK, Yip AW, Szeto ML, Li KF, Lau P, Fung FM, Tong TS, Lai KC, Hu WH, Yuen MF, Hui CK, Lam SK. Rabeprazole-based 3-day and 7-day triple therapy vs. omeprazole-based 7-day triple therapy for the treatment of Helicobacter pylori infection. Aliment Pharmacol Ther 2001; 15:1959-65. [PMID: 11736727 DOI: 10.1046/j.1365-2036.2001.01118.x] [Citation(s) in RCA: 25] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/21/2022]
Abstract
BACKGROUND Rabeprazole is a new proton pump inhibitor with more potent acid suppressive and anti-Helicobacter effects. AIM To compare two different regimens of rabeprazole-based triple therapy vs. 7-day omeprazole-based triple therapy for the eradication of Helicobacter pylori infection. METHOD Patients with proven H. pylori infection were randomized to receive: (i) 7-day rabeprazole, 10 mg, amoxicillin, 1000 mg, and clarithromycin, 500 mg, all twice daily; (ii) 3-day rabeprazole, 20 mg, amoxicillin, 1000 mg, and clarithromycin, 500 mg, all twice daily; or (iii) 7-day omeprazole, 20 mg, amoxicillin, 1000 mg, and clarithromycin, 500 mg, all twice daily. Endoscopy (CLO test, histology) was performed before randomization and 6 weeks after drug treatment. RESULTS One hundred and seventy-three patients were randomized. H. pylori eradication rates (intention-to-treat, n=173/per protocol, n=167) were 88%/91% for 7-day rabeprazole-based therapy, 72%/72% for 3-day rabeprazole-based therapy and 82%/89% for 7-day omeprazole-based therapy, respectively. The per protocol eradication rate was significantly better in the 7-day rabeprazole-based therapy and 7-day omeprazole-based therapy groups when compared to the 3-day rabeprazole-based therapy group (P=0.01 and P=0.04, respectively). Compliance was excellent and all three regimens were well tolerated. CONCLUSIONS The efficacy of seven-day rabeprazole-based triple therapy is similar to 7-day omeprazole-based triple therapy for the eradication of H. pylori infection.
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Affiliation(s)
- B C Wong
- Department of Medicine, University of Hong Kong, Queen Mary Hospital, Hong Kong.
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