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For: Nakajima A, Seki M, Taniguchi S. Determining an optimal clinical dose of elobixibat, a novel inhibitor of the ileal bile acid transporter, in Japanese patients with chronic constipation: a phase II, multicenter, double-blind, placebo-controlled randomized clinical trial. J Gastroenterol 2018;53:525-34. [PMID: 28840422 DOI: 10.1007/s00535-017-1383-5] [Citation(s) in RCA: 42] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [What about the content of this article? (0)] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/07/2017] [Accepted: 08/09/2017] [Indexed: 02/04/2023]

For:	Nakajima A, Seki M, Taniguchi S. Determining an optimal clinical dose of elobixibat, a novel inhibitor of the ileal bile acid transporter, in Japanese patients with chronic constipation: a phase II, multicenter, double-blind, placebo-controlled randomized clinical trial. J Gastroenterol 2018;53:525-34. [PMID: 28840422 DOI: 10.1007/s00535-017-1383-5] [Citation(s) in RCA: 42] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [What about the content of this article? (0)] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/07/2017] [Accepted: 08/09/2017] [Indexed: 02/04/2023]

Number

Cited by Other Article(s)

Sakai Y, Tsuyuguchi T, Kumagai J, Ohyama H, Kaiho T, Ohtsuka M, Kato N. Efficacy of elobixibat for elderly patients with chronic constipation in a clinic. World J Gastrointest Pharmacol Ther 2025;16:105801. [DOI: 10.4292/wjgpt.v16.i2.105801] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/06/2025] [Revised: 03/07/2025] [Accepted: 04/01/2025] [Indexed: 06/03/2025] Open

Abstract

BACKGROUND

Elobixibat reportedly improves bowel movements in patients with chronic constipation. However, its effect on bowel movements in elderly patients with chronic constipation in clinical settings has not been examined.

AIM

To examine bowel movement frequency and stool form before and after elobixibat administration in elderly patients with chronic constipation at our clinic.

METHODS

A total of 10 mg elobixibat was administered to 35 (< 65 years old) patients and 45 (≥ 65 years old) patients with chronic constipation. The frequency of bowel movements and stool forms, assessed using the Bristol Stool Form Scale (BSFS), were compared between the two groups 1 week before and after elobixibat administration.

RESULTS

In patients aged < 65 years with chronic constipation, the pre-elobixibat frequency of bowel movements and BSFS scores were 2.167 ± 0.732 and 2.286 ± 0.742, respectively. After elobixibat administration, the frequency of bowel movements and BSFS scores improved to 2.389 ± 0.502 and 3.995 ± 0.566, respectively, showing a significant improvement in bowel movement status. In patients aged ≥ 65 years with chronic constipation, the pre-elobixibat frequency of bowel movements and BSFS scores were 2.003 ± 0.733 and 2.217 ± 0.758, respectively. After elobixibat administration, the frequency of bowel movements and BSFS scores improved to 4.402 ± 1.346 and 3.800 ± 0.704, respectively, indicating an improvement in bowel movement status (P < 0.001). No significant differences were observed in the frequency and improvement status of bowel movements or BSFS scores between patients with chronic constipation aged ≥ 65 years and < 65 years. Adverse events due to the administration of elobixibat occurred in 16 cases (20%). No significant differences were found in the incidence of adverse events between patients with chronic constipation aged < 65 years (8 cases, 22.9%) and those aged ≥ 65 years (8 cases, 17.8%).

CONCLUSION

Elobixibat is effective in improving bowel movement status in patients with chronic constipation. No significant differences were found in the improvement of bowel movement status or the incidence of adverse events between patients with chronic constipation aged < 65 years and ≥ 65 years, suggesting that the drug may be safely used in elderly patients.

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Rezk MR, Soliman M, Shawky H, Badr KA, Wadie M. A novel ultra-sensitive LC-MS/MS method for determination of elobixibat in human plasma; Application to a bioequivalence study on healthy volunteers. J Chromatogr B Analyt Technol Biomed Life Sci 2025;1257:124576. [PMID: 40163983 DOI: 10.1016/j.jchromb.2025.124576] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/24/2025] [Revised: 03/24/2025] [Accepted: 03/24/2025] [Indexed: 04/02/2025]

Nakajima A, Umeyama M, Higashikawa M, Shimada Y, Arai Y. A multicenter, postmarketing surveillance of elobixibat in patients with chronic constipation in Japan: A final analysis report. SAGE Open Med 2025;13:20503121251321659. [PMID: 40012762 PMCID: PMC11863239 DOI: 10.1177/20503121251321659] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/12/2024] [Accepted: 02/03/2025] [Indexed: 02/28/2025] Open

Abstract

Objective

An interim analysis of postmarketing surveillance reported the safety and efficacy of elobixibat, a laxative medication that inhibits the ileal bile acid transporter, at 4 weeks in approximately 1000 patients with chronic constipation in Japan. However, its long-term safety and efficacy in elderly patients remain unclear. This study aimed to conclude and report the final analysis of postmarketing surveillance, including 52-week safety and efficacy profiles in a clinical practice setting, using approximately 3000 patients.

Methods

The overall survey period spanned from June 2018 to May 2022. Observation periods were set at 4 weeks (4-week treatment period) and 52 weeks (52-week treatment period). Adverse drug reactions and efficacy outcomes, including defecation frequency, Bristol Stool Form Scale scores, and patient satisfaction, were analyzed.

Results

The 4-week safety analysis set included 3638 patients with a mean age of 70.8 years, and 73.7% were aged ⩾65 years. Most patients (62.5%) were treated with elobixibat alone, while the rest received concomitant laxatives. In total, 231 patients (6.35%) experienced adverse drug reactions, with gastrointestinal disorders (6.02%) such as diarrhea (3.35%) and abdominal pain (2.06%), being the most common adverse drug reaction. The adverse drug reaction incidence in elderly patients aged ⩾65, ⩾75, and ⩾85 years was 5.49%, 4.85%, and 2.80%, respectively. In the 52-week treatment period, adverse drug reaction incidence was 5.40% (71/1315 patients), similar to that in the 4-week treatment period. Regarding efficacy, defecation frequency and Bristol Stool Form Scale scores significantly improved from week 2 onward, regardless of the age group and administration timing (before breakfast, lunch, or dinner). Most patients reported satisfaction from week 2 onward (6.0%, 66.9%, 78.6%, and 90.4% at baseline, weeks 2, 4, and 52, respectively).

Conclusion

This study confirmed the long-term safety and efficacy of elobixibat in patients with chronic constipation, including many elderly ones, in routine clinical practice.

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Agarwal P, Jha BK, Somagoni J, B SS, Modh V, Chakilam SK, Kumar V, Vasantrao MS, Kalla M, Kavitha A, Goyal O, Bhatia A. Efficacy and safety of elobixibat in patients with chronic constipation-A randomized, multicenter, double-blind, placebo-controlled, parallel-group study from India. Indian J Gastroenterol 2025:10.1007/s12664-024-01719-7. [PMID: 39985701 PMCID: PMC12141165 DOI: 10.1007/s12664-024-01719-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/12/2024] [Accepted: 11/21/2024] [Indexed: 02/24/2025]

Abstract

BACKGROUND

Elobixibat is a locally acting ileal bile acid transporter (IBAT) inhibitor that relieves functional constipation in patients by accelerating colonic transit. In this study, we aimed at determining the efficacy and safety of elobixibat for short-term treatment (two weeks) of chronic constipation in Indian patients.

METHODS

The present study was a randomized, double-blind, parallel-group, placebo-controlled, phase III study to evaluate efficacy and safety of elobixibat. The study planned to enroll patients with chronic constipation of at least six months' duration, satisfying Rome IV criteria for functional constipation. Following a run-in of approximately 14 days to confirm eligibility and determine baseline frequency of spontaneous bowel movements (SBMs), eligible patients were randomized 1:1 either to elobixibat or to placebo groups. The change in weekly frequency of spontaneous bowel movements (SBMs) at the end of treatment (week two) over baseline was the primary efficacy endpoint in this trial. Primary efficacy analyses were based on the modified intention-to-treat (mITT) population. This trial is registered at CTRI (Clinical Trial Registry of India).

RESULTS

Between April 2023 and December 2023, 150 patients were randomized into the two-week trial. In mITT population (n = 146 [elobixibat = 75 and placebo = 71]), the least square mean (LSM) difference between elobixibat (3.83) and placebo (2.68) was 1.15 (95% CI, 0.31, 1.99) demonstrating a statistically significant improvement (p = 0.008) in weekly frequency of SBMs (week two over baseline) with the use of elobixibat. The proportions of patients with a complete spontaneous bowel movement (CSBM) "response" was significantly higher with elobixibat (49.33%) compared to the placebo (26.76%) treatment (difference 22.57% [95% CI, 8.36%, 36.78%] [p = 0.005]). The most common adverse event (AE) was abdominal pain (elobixibat = 6 patients [7.89%] vs. placebo = 3 patients [4.05%]).

CONCLUSIONS

Elobixibat was well tolerated and improved bowel movement frequency within two weeks of treatment in Indian patient population with chronic constipation.

CLINICAL TRIAL REGISTRY NUMBER

CTRI/2022/10/046690.

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Sakai Y, Tsuyuguchi T, Kumagai J, Ohyama H, Kaiho T, Ohtsuka M, Kato N. Usefulness of Elobixibat in Patients With Chronic Constipation After Cholecystectomy. Cureus 2024;16:e67132. [PMID: 39156998 PMCID: PMC11330673 DOI: 10.7759/cureus.67132] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 06/29/2024] [Indexed: 08/20/2024] Open

Abstract

BACKGROUND

There have been reports that elobixibat improves bowel movements in patients with chronic constipation. However, no studies have been conducted to date to examine bowel movements after the administration of elobixibat in patients with chronic constipation in terms of the presence or absence of the gallbladder. In this study, we examined the frequency of bowel movements and stool forms in patients with gallbladders and post-cholecystectomy patients before and after the administration of elobixibat for chronic constipation.

METHODS

Elobixibat 10 mg was administered to treat chronic constipation in 40 patients with gallbladders and 18 patients who underwent cholecystectomy. The frequencies of bowel movements one week before and after elobixibat administration were compared between the two groups, using the Bristol Stool Form Scale (BSFS).

RESULTS

No significant difference in patient background with or without cholecystectomy was noted between the groups. In patients with gallbladders, the pre-dosing mean frequency of bowel movements was 2.389 ± 0.502 with BSFS of 2.179 ± 0.721 and the post-dosing mean frequency of bowel movements was 4.308 ± 1.151 with BSFS of 3.718 ± 1.521, indicating significant improvement in bowel movements (p < 0.001). In post-cholecystectomy patients, the pre-dosing mean frequency of bowel movements was 2.389 ± 0.502 with BSFS of 2.222 ± 0.647 and the post-dosing mean frequency of bowel movements was 4.222 ± 1.734 with BSFS of 3.333±1.237, indicating significant improvement in bowel movements (p < 0.001). No significant difference in bowel movements was noted between patients with or without the gallbladder.

CONCLUSIONS

Elobixibat is useful in improving the bowel movements of patients with chronic constipation. No significant difference was noted in the improvement of bowel movements due to cholecystectomy. It was suggested that even post-cholecystectomy patients could obtain therapeutic effects similar to patients with gallbladders.

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Wang K, Qiu H, Chen F, Cai P, Qi F. Considering traditional Chinese medicine as adjunct therapy in the management of chronic constipation by regulating intestinal flora. Biosci Trends 2024;18:127-140. [PMID: 38522913 DOI: 10.5582/bst.2024.01036] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/26/2024]

Abstract

Chronic constipation is one of the most common gastrointestinal disorders worldwide. Due to changes in diet, lifestyle, and the aging population, the incidence of chronic constipation has increased year by year. It has had an impact on daily life and poses a considerable economic burden. Nowadays, many patients with chronic constipation try to seek help from complementary and alternative therapies, and traditional Chinese medicine (TCM) is often their choice. The intestinal flora play an important role in the pathogenesis of constipation by affecting the body's metabolism, secretion, and immunity. Regulating the intestinal flora and optimizing its composition might become an important prevention and treatment for chronic constipation. TCM has unique advantages in regulating the imbalance of intestinal flora, and its curative effect is precise. Therefore, we reviewed the relationship between intestinal flora and chronic constipation as well as advances in research on TCM as adjunct therapy in the management of chronic constipation by regulating intestinal flora. Some single Chinese herbs and their active ingredients (e.g., Rheum palmatum, Radix Astragalus, and Cistanche deserticola), some traditional herbal formulations (e.g., Jichuan decoction, Zengye decoction, and Zhizhu decoction) and some Chinese patent medicines (e.g., Maren pills and Shouhui Tongbian capsules) that are commonly used to treat chronic constipation by regulating intestinal flora are highlighted and summarized. Moreover, some external forms of TCM, and especially acupuncture, have also been found to improve intestinal movement and alleviate constipation symptoms by regulating intestinal flora. We hope this review can contribute to an understanding of TCM as an adjunct therapy for chronic constipation and that it can provide useful information for the development of more effective constipation therapies.

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Hatano T, Oyama G, Shimo Y, Ogaki K, Nishikawa N, Nakamura R, Tsunemi T, Ogawa T, Eguchi H, Daida K, Kurita N, Ueno SI, Fukae J, Sako W, Shiina K, Nakajima S, Oji Y, Wakamori R, Saiki S, Nishioka K, Okuzumi A, Taniguchi D, Takeshige-Amano H, Fuse A, Nakajima A, Kano M, Kamo H, Yamashita Y, Shindo A, Yanagisawa N, Hattori N. Efficacy and Safety of Elobixibat in Parkinson's Disease with Chronic Constipation: CONST-PD Study. Mov Disord Clin Pract 2024;11:352-362. [PMID: 38264844 PMCID: PMC10982595 DOI: 10.1002/mdc3.13972] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/05/2023] [Revised: 11/28/2023] [Accepted: 12/28/2023] [Indexed: 01/25/2024] Open

Abstract

BACKGROUND

Chronic constipation is a common digestive complication of Parkinson's disease (PD).

OBJECTIVES

To verify the usefulness of elobixibat, an ileal bile acid transporter inhibitor, for chronic constipation in PD.

METHODS

This double-blind, placebo-controlled study consisted of a 2-week observation/washout period and a 4-week treatment period. All patients received a Bowel Movement Diary at Week -2 and were allocated to elobixibat (10 mg) or placebo at Week 0. Patients visited at Weeks 2 and 4 to report daily spontaneous bowel movements (SBM), stool form, drug use, quality of life (QOL), and safety. Changes in these parameters were assessed.

RESULTS

The study included 38 patients in the elobixibat group and 39 in the placebo group, and 37 each completed the study. SBM frequency/week (mean ± standard deviation) increased significantly from 4.2 ± 2.6 at baseline to 5.9 ± 3.2 at Week 4 in the elobixibat group (P = 0.0079), but not in the placebo group (4.5 ± 2.7 to 5.3 ± 3.5; P = 0.0889). On analysis of covariance, the between-group difference in frequency changes at Week 4 (primary endpoint) was not significant after adjustment by baseline and sex (point estimate = 0.8; 95% confidence interval = -0.57 to 2.09, P = 0.2601), although a significant difference (P = 0.0011) was evidenced at Week 1 by a similar analysis. Stool form and scores of satisfaction and stigma were improved by elobixibat. Adverse events were as previously reported.

CONCLUSIONS

Elobixibat improved the SBM frequency, though the defined primary endpoint was not evidenced. QOL parameters (stool consistency and treatment satisfaction) were also improved. Elobixibat may have therapeutic benefits in PD patients suffering from chronic constipation.

TRIAL REGISTRATION INFORMATION

Trial Registration Number: JPRN-jRCTs031200172 (submitted: October 26, 2020; first patient enrolment: December 23, 2020; https://jrct.niph.go.jp/en-latest-detail/jRCTs031200172).

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Affiliation(s)

Taku Hatano Department of Neurology, Juntendo University Faculty of Medicine, Tokyo, Japan
Genko Oyama Department of Neurology, Juntendo University Faculty of Medicine, Tokyo, Japan
Yasushi Shimo Department of Neurology, Juntendo Nerima Hospital, Tokyo, Japan
Kotaro Ogaki Department of Neurology, Juntendo Urayasu Hospital, Urayasu, Japan
Noriko Nishikawa Department of Neurology, Juntendo University Faculty of Medicine, Tokyo, Japan
Ryota Nakamura Department of Neurology, Juntendo Urayasu Hospital, Urayasu, Japan
Taiji Tsunemi Department of Neurology, Juntendo University Faculty of Medicine, Tokyo, Japan
Takashi Ogawa Department of Neurology, Juntendo Urayasu Hospital, Urayasu, Japan
Hiroto Eguchi Department of Neurology, Juntendo Nerima Hospital, Tokyo, Japan
Kensuke Daida Department of Neurology, Juntendo University Faculty of Medicine, Tokyo, Japan
Naohide Kurita Department of Neurology, Juntendo Urayasu Hospital, Urayasu, Japan
Shin-Ichi Ueno Department of Neurology, Juntendo University Faculty of Medicine, Tokyo, Japan
Jiro Fukae Department of Neurology, Juntendo Nerima Hospital, Tokyo, Japan
Wataru Sako Department of Neurology, Juntendo University Faculty of Medicine, Tokyo, Japan
Kenta Shiina Department of Neurology, Juntendo University Faculty of Medicine, Tokyo, Japan
Sho Nakajima Department of Neurology, Juntendo Urayasu Hospital, Urayasu, Japan
Yutaka Oji Department of Neurology, Juntendo University Faculty of Medicine, Tokyo, Japan
Ryo Wakamori Department of Neurology, Juntendo University Faculty of Medicine, Tokyo, Japan
Shinji Saiki Department of Neurology, Juntendo University Faculty of Medicine, Tokyo, Japan
Kenya Nishioka Department of Neurology, Juntendo University Faculty of Medicine, Tokyo, Japan
Ayami Okuzumi Department of Neurology, Juntendo University Faculty of Medicine, Tokyo, Japan
Daisuke Taniguchi Department of Neurology, Juntendo University Faculty of Medicine, Tokyo, Japan
Haruka Takeshige-Amano Department of Neurology, Juntendo University Faculty of Medicine, Tokyo, Japan
Atsuhito Fuse Department of Neurology, Juntendo Nerima Hospital, Tokyo, Japan
Asuka Nakajima Department of Neurology, Juntendo Nerima Hospital, Tokyo, Japan
Masayoshi Kano Department of Neurology, Juntendo Nerima Hospital, Tokyo, Japan
Hikaru Kamo Department of Neurology, Juntendo University Faculty of Medicine, Tokyo, Japan
Yuri Yamashita Department of Neurology, Juntendo University Faculty of Medicine, Tokyo, Japan
Atsuhiko Shindo Department of Neurology, Juntendo University Faculty of Medicine, Tokyo, Japan
Naotake Yanagisawa Juntendo Clinical Research and Trial Center, Juntendo University Hospital, Tokyo, Japan
Nobutaka Hattori Department of Neurology, Juntendo University Faculty of Medicine, Tokyo, Japan

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Fujisue K, Ito M, Matsuzawa Y, Arima Y, Takashio S, Sueta D, Araki S, Hanatani S, Yamanaga K, Yamamoto M, Kaneko S, Yamamoto E, Matsushita K, Soejima H, Tsujita K. Open-Label, Single-Center, Single-Arm Study Evaluating the Efficacy and Safety of Elobixibat for Chronic Constipation in Patients With Heart Failure. Circ Rep 2024;6:55-63. [PMID: 38464992 PMCID: PMC10920016 DOI: 10.1253/circrep.cr-23-0099] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/05/2024] [Accepted: 01/05/2024] [Indexed: 03/12/2024] Open

Affiliation(s)

Koichiro Fujisue Department of Cardiovascular Medicine, Graduate School of Medical Sciences, Kumamoto University Kumamoto Japan
Miwa Ito Department of Cardiovascular Medicine, Graduate School of Medical Sciences, Kumamoto University Kumamoto Japan Miyazaki Medical Association Hospital Miyazaki Japan
Yasushi Matsuzawa Department of Cardiovascular Medicine, Graduate School of Medical Sciences, Kumamoto University Kumamoto Japan
Yuichiro Arima Department of Cardiovascular Medicine, Graduate School of Medical Sciences, Kumamoto University Kumamoto Japan
Seiji Takashio Department of Cardiovascular Medicine, Graduate School of Medical Sciences, Kumamoto University Kumamoto Japan
Daisuke Sueta Department of Cardiovascular Medicine, Graduate School of Medical Sciences, Kumamoto University Kumamoto Japan
Satoshi Araki Department of Cardiovascular Medicine, Graduate School of Medical Sciences, Kumamoto University Kumamoto Japan
Shinsuke Hanatani Department of Cardiovascular Medicine, Graduate School of Medical Sciences, Kumamoto University Kumamoto Japan
Kenshi Yamanaga Department of Cardiovascular Medicine, Graduate School of Medical Sciences, Kumamoto University Kumamoto Japan
Masahiro Yamamoto Department of Cardiovascular Medicine, Graduate School of Medical Sciences, Kumamoto University Kumamoto Japan
Shozo Kaneko Department of Cardiovascular Medicine, Graduate School of Medical Sciences, Kumamoto University Kumamoto Japan
Eiichiro Yamamoto Department of Cardiovascular Medicine, Graduate School of Medical Sciences, Kumamoto University Kumamoto Japan
Kenichi Matsushita Department of Cardiovascular Medicine, Graduate School of Medical Sciences, Kumamoto University Kumamoto Japan Department of Cardiology, Saitama Medical University International Medical Center Hidaka Japan
Hirofumi Soejima Department of Cardiovascular Medicine, Graduate School of Medical Sciences, Kumamoto University Kumamoto Japan
Kenichi Tsujita Department of Cardiovascular Medicine, Graduate School of Medical Sciences, Kumamoto University Kumamoto Japan

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Rao SS, Manabe N, Karasawa Y, Hasebe Y, Nozawa K, Nakajima A, Fukudo S. Comparative profiles of lubiprostone, linaclotide, and elobixibat for chronic constipation: a systematic literature review with meta-analysis and number needed to treat/harm. BMC Gastroenterol 2024;24:12. [PMID: 38166671 PMCID: PMC10759335 DOI: 10.1186/s12876-023-03104-8] [Citation(s) in RCA: 7] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/14/2023] [Accepted: 12/19/2023] [Indexed: 01/05/2024] Open

Masaoka T. Current Management of Chronic Constipation in Japan. Keio J Med 2023;72:95-101. [PMID: 37612093 DOI: 10.2302/kjm.2022-0036-ir] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 08/25/2023]

Bassotti G, Usai Satta P, Berti G, Lai M, Villanacci V, Bellini M. Pharmacotherapeutic advances for chronic idiopathic constipation in adults. Expert Opin Pharmacother 2022;23:2053-2078. [PMID: 36408585 DOI: 10.1080/14656566.2022.2150076] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/09/2021] [Accepted: 11/17/2022] [Indexed: 11/22/2022]

Hishida Y, Nagai Y, Tsukiyama H, Nakamura Y, Nakagawa T, Ishizaki S, Tanaka Y, Sone M. Effects of Elobixibat in Patients with Diabetes and Concomitant Chronic Constipation: an 8-week, Prospective, Single-center, Single-arm Study. Adv Ther 2022;39:4205-4217. [PMID: 35867276 PMCID: PMC9402500 DOI: 10.1007/s12325-022-02243-w] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/29/2022] [Accepted: 06/23/2022] [Indexed: 11/01/2022]

Elwing JE, Atassi H, Rogers BD, Sayuk GS. Emerging therapies in the management of Irritable Bowel Syndrome (IBS). Expert Opin Emerg Drugs 2022;27:55-73. [PMID: 35266839 DOI: 10.1080/14728214.2022.2052043] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/04/2022]

Hatano T, Oyama G, Shimo Y, Ogaki K, Nishikawa N, Fukae J, Nakamura R, Kurita N, Tsunemi T, Oji Y, Saiki S, Nishioka K, Takeshige-Amano H, Taniguchi D, Ogawa T, Kamo H, Eguchi H, Fuse A, Nakajima A, Kano M, Nakajima S, Yanagisawa N, Hattori N. Investigating the efficacy and safety of elobixibat, an ileal bile acid transporter inhibitor, in patients with Parkinson's disease with chronic constipation: a multicentre, placebo-controlled, randomised, double-blind, parallel-group stud (CONST-PD). BMJ Open 2022;12:e054129. [PMID: 35149566 PMCID: PMC8845182 DOI: 10.1136/bmjopen-2021-054129] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/22/2022] Open

Abstract

INTRODUCTION

Chronic constipation worsens the quality of life (QOL) of patients with Parkinson's disease (PD). Elobixibat, an ileal bile acid transporter inhibitor, is a useful laxative, but its effect on chronic constipation in patients with PD remains unclear. Therefore, we designed a placebo-controlled, randomised, double-blind study to investigate the efficacy and safety of elobixibat in patients with PD with chronic constipation.

METHODS AND ANALYSIS

The study will consist of 2-week observation and 4-week treatment periods. Patients with clinically established PD will record the status of spontaneous bowel movements and use of rescue medications/concomitant medications in a Bowel Movement Diary from the start of the observation period at visit 1 (week -2). At visit 2 (week 0), patients will be assessed for final registration based on the diary records and physical examinations, and allocated to either the elobixibat or placebo group. Daily intake of the investigational drug will be recorded in the diary. Patients will undergo laboratory tests and answer constipation-related, PD-related and QOL-related questionnaires at visits 2 and 4 (week 4). Subjective symptoms and objective findings will be collected at visits 2, 3 (week 2) and 4. Since patients' motor function might be improved by treatment of constipation, the use of dopamine preparations will also be monitored. Bowel movement data and other parameters will be compared between groups.Safety information will be collected as adverse events, specifically focusing on those occurring in association with study conduct.

ETHICS AND DISSEMINATION

This study will be conducted in accordance with the Helsinki Declaration, the Clinical Trials Act of the Japan Ministry of Health, Labour and Welfare, and related laws and regulations. The study was approved by the Juntendo University Certified Review Board. The results will be disseminated through an online study registry (Japan Registry of Clinical Trials), presented at scientific conferences, and published in medical journals.

TRIAL REGISTRATION NUMBER

JPRN-jRCTs031200172; Pre-results.

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Keely SJ, Urso A, Ilyaskin AV, Korbmacher C, Bunnett NW, Poole DP, Carbone SE. Contributions of bile acids to gastrointestinal physiology as receptor agonists and modifiers of ion channels. Am J Physiol Gastrointest Liver Physiol 2022;322:G201-G222. [PMID: 34755536 PMCID: PMC8782647 DOI: 10.1152/ajpgi.00125.2021] [Citation(s) in RCA: 17] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/02/2021] [Revised: 10/28/2021] [Accepted: 11/08/2021] [Indexed: 02/03/2023]

Yamaguchi D, Hidaka H, Matsunaga T, Akutagawa T, Tanaka Y, Jubashi A, Takeuchi Y, Tsuruoka N, Sakata Y, Miyahara K, Tominaga N, Kawakubo H, Takamori A, Shimoda R, Noda T, Ogata S, Tsunada S, Esaki M. Efficacy of elobixibat as bowel preparation agent for colonoscopy: Prospective, randomized, multi-center study. Dig Endosc 2022;34:171-179. [PMID: 33971037 PMCID: PMC9290049 DOI: 10.1111/den.14010] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/13/2020] [Revised: 04/30/2021] [Accepted: 05/06/2021] [Indexed: 01/27/2023]

Affiliation(s)

Daisuke Yamaguchi Department of GastroenterologyNational Hospital Organization Ureshino Medical CenterSagaJapan,Division of GastroenterologyDepartment of Internal MedicineFaculty of MedicineSaga UniversitySagaJapan
Hidenori Hidaka Department of Internal MedicineKaratsu Red Cross HospitalSagaJapan
Takuya Matsunaga Department of GastroenterologySaga‐ken Medical Centre KoseikanSagaJapan
Takashi Akutagawa Division of GastroenterologyDepartment of Internal MedicineFaculty of MedicineSaga UniversitySagaJapan
Yuichiro Tanaka Department of GastroenterologyNational Hospital Organization Ureshino Medical CenterSagaJapan,Department of Internal MedicineImari‐Arita Kyoritsu HospitalSagaJapan
Amane Jubashi Department of GastroenterologyNational Hospital Organization Ureshino Medical CenterSagaJapan
Yuki Takeuchi Department of GastroenterologyNational Hospital Organization Ureshino Medical CenterSagaJapan
Nanae Tsuruoka Division of GastroenterologyDepartment of Internal MedicineFaculty of MedicineSaga UniversitySagaJapan
Yasuhisa Sakata Division of GastroenterologyDepartment of Internal MedicineFaculty of MedicineSaga UniversitySagaJapan
Koichi Miyahara Department of Internal MedicineKaratsu Red Cross HospitalSagaJapan
Naoyuki Tominaga Department of GastroenterologySaga‐ken Medical Centre KoseikanSagaJapan
Hiroharu Kawakubo Department of Internal MedicineImari‐Arita Kyoritsu HospitalSagaJapan
Ayako Takamori Clinical Research CenterSaga University HospitalSagaJapan
Ryo Shimoda Division of GastroenterologyDepartment of Internal MedicineFaculty of MedicineSaga UniversitySagaJapan
Takahiro Noda Department of Internal MedicineKaratsu Red Cross HospitalSagaJapan
Shinichi Ogata Department of GastroenterologySaga‐ken Medical Centre KoseikanSagaJapan
Seiji Tsunada Department of GastroenterologyNational Hospital Organization Ureshino Medical CenterSagaJapan
Motohiro Esaki Division of GastroenterologyDepartment of Internal MedicineFaculty of MedicineSaga UniversitySagaJapan

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A Systematic Review and Network Meta-Analysis on the Efficacy of Medications in the Treatment of Chronic Idiopathic Constipation in Japan. Gastroenterol Res Pract 2021;2021:5534687. [PMID: 34887919 PMCID: PMC8651382 DOI: 10.1155/2021/5534687] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/28/2021] [Revised: 10/27/2021] [Accepted: 10/30/2021] [Indexed: 11/24/2022] Open

Abstract

Background

In the 2010s, medications with new mechanisms were introduced in Japan for the treatment of chronic idiopathic constipation (CIC). A few systematic reviews have compared medications' relative efficacy, but the reviews included studies on patients from various races, even though the mechanism of CIC is considered to differ between races. The aim of this study was to use a systematic review and network meta-analysis to compare the relative efficacy of these medications in Japanese patients.

Methods

We conducted a meta-analysis and report it here according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). We identified studies by searching MEDLINE (via the PubMed interface) and the Cochrane Library and ICHUSHI databases and included randomized clinical trials that compared medications for CIC with placebo in Japanese adults. Two reviewers independently screened and assessed articles, abstracted data, and assessed the risk of bias. We pooled data by random-effects meta-analyses and also performed a Bayesian network meta-analysis to indirectly compare data.

Results

The present systematic review and meta-analyses included 1460 patients in 6 randomized clinical trials: 2 on linaclotide, 3 on elobixibat, 2 on lubiprostone, and 1 on lactulose. The results of direct comparisons showed that linaclotide, elobixibat, and lubiprostone were superior to placebo in the change of spontaneous bowel movements (SBMs) within 1 week: linaclotide, 1.95 (95% CI, 1.51-2.39); elobixibat, 5.69 (95% CI, 3.31-8.07); and lubiprostone, 2.41 (95% CI, 0.82-4.01). The Bayesian network meta-analysis showed consistent results. Elobixibat 10 mg was ranked first for the increase in SBMs and complete SBMs within 1 week and the time to first SBM. Lubiprostone 48 μg was ranked first for the proportion of patients with SBM within 24 hours.

Conclusion

Our direct and indirect meta-analyses revealed that the new CIC medications available in Japan have equal efficacy but that elobixibat and lubiprostone are highly likely to be more efficacious.

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Bassotti G, Usai Satta P, Bellini M. Chronic Idiopathic Constipation in Adults: A Review on Current Guidelines and Emerging Treatment Options. Clin Exp Gastroenterol 2021;14:413-428. [PMID: 34712055 PMCID: PMC8547593 DOI: 10.2147/ceg.s256364] [Citation(s) in RCA: 19] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/11/2021] [Accepted: 09/28/2021] [Indexed: 12/12/2022] Open

Ozaki A, Kessoku T, Kasai Y, Takeda Y, Okubo N, Iwaki M, Kobayashi T, Yoshihara T, Honda Y, Fuyuki A, Higurashi T, Ishiki H, Taguri M, Oyamada S, Kobayashi N, Nakajima A, Ichikawa Y. Elobixibat Effectively Relieves Chronic Constipation in Patients with Cancer Regardless of the Amount of Food Intake. Oncologist 2021;26:e1862-e1869. [PMID: 34180099 PMCID: PMC8488789 DOI: 10.1002/onco.13879] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/23/2020] [Accepted: 06/18/2021] [Indexed: 12/21/2022] Open

Abstract

BACKGROUND

Constipation is a common, distressing complication in patients with cancer receiving palliative care. Elobixibat is a novel inhibitor of the ileal bile acid transporter that is used to treat chronic constipation by stimulating bowel function. However, its efficacy in patients with cancer has not been examined. This study investigated the drug's effectiveness in patients with cancer with chronic constipation.

PATIENTS AND METHODS

This prospective-sampling, single-center, observational study included hospitalized patients with cancer diagnosed, using the Rome IV criteria, with chronic constipation. Within 2 weeks of hospitalization, each participant was administered elobixibat (5-15 mg) daily until discharge. Spontaneous bowel movements (SBMs), complete spontaneous bowel movements (CSBMs), Bristol stool form scale (BSFS) scores, and the Patient Assessment of Constipation Quality of Life questionnaire (PAC-QOL) scores were assessed before and after elobixibat administration. We also evaluated the relationship between the amount of food consumed and the SBM frequency.

RESULTS

Among the 83 participants, the mean pre- and post-treatment frequencies of daily SBMs were 0.3 and 1.2 (p < .0001) and those of CSBMs were 0.1 and 0.6 (p < .0001), respectively. The mean pretreatment BSFS score was 1.6, whereas the post-treatment value was 3.5 (p < .0001); the mean PAC-QOL score (overall) improved from 1.01 to 0.74 (p = .01). There was no significant change in the daily SBM frequency between fasting and feeding states (1.2 vs. 1.3; p = .8), and there was no correlation between the amount of food intake and the SBM frequency after elobixibat administration (r = .03). Serious adverse events were not observed.

CONCLUSION

This study showed that elobixibat is safe and effective for patients with cancer with chronic constipation, regardless of the food intake amount.

IMPLICATIONS FOR PRACTICE

Elobixibat was effective at relieving chronic constipation in patients with various cancers. Serious adverse events were not observed, and the relief of constipation was independent of variation in food intake.

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Affiliation(s)

Anna Ozaki Department of Gastroenterology and Hepatology, Yokohama City UniversityYokohamaJapan
Takaomi Kessoku Department of Gastroenterology and Hepatology, Yokohama City UniversityYokohamaJapan Department of Palliative Medicine, Yokohama City UniversityYokohamaJapan
Yuki Kasai Department of Gastroenterology and Hepatology, Yokohama City UniversityYokohamaJapan
Yuma Takeda Department of Oncology, Yokohama City UniversityYokohamaJapan
Naoki Okubo Department of Oncology, Yokohama City UniversityYokohamaJapan
Michihiro Iwaki Department of Gastroenterology and Hepatology, Yokohama City UniversityYokohamaJapan
Takashi Kobayashi Department of Gastroenterology and Hepatology, Yokohama City UniversityYokohamaJapan
Tsutomu Yoshihara Department of Gastroenterology and Hepatology, Yokohama City UniversityYokohamaJapan Department of Palliative Medicine, Yokohama City UniversityYokohamaJapan
Yasushi Honda Department of Gastroenterology and Hepatology, Yokohama City UniversityYokohamaJapan Department of Palliative Medicine, Yokohama City UniversityYokohamaJapan
Akiko Fuyuki Department of Gastroenterology and Hepatology, Yokohama City UniversityYokohamaJapan Department of Palliative Medicine, Yokohama City UniversityYokohamaJapan
Takuma Higurashi Department of Gastroenterology and Hepatology, Yokohama City UniversityYokohamaJapan
Hiroto Ishiki Department of Palliative Medicine, National Cancer Center HospitalTokyoJapan
Masataka Taguri Department of Data Science, Yokohama City University Graduate School of MedicineYokohamaJapan
Shunsuke Oyamada Department of Biostatistics, Japanese Organization for Research and Treatment of Cancer (JORTC), JORTC Data CenterTokyoJapan
Noritoshi Kobayashi Department of Oncology, Yokohama City UniversityYokohamaJapan
Atsushi Nakajima Department of Gastroenterology and Hepatology, Yokohama City UniversityYokohamaJapan
Yasushi Ichikawa Department of Oncology, Yokohama City UniversityYokohamaJapan

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Yamada E, Tsunoda S, Mimura M, Akizuki M, Miyazawa Y, Yamazaki T, Nagano Y, Murakami R, Kitahara T, Wakasugi J, Ozawa Y, Komatsu T, Inamori M, Nagai K, Nakajima A. Positioning of Bristol Stool Form Scale type 3 in constipation treatment satisfaction: A multicenter study in Japan. J Gastroenterol Hepatol 2021;36:2125-2130. [PMID: 33538361 DOI: 10.1111/jgh.15428] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/28/2020] [Revised: 12/14/2020] [Accepted: 01/31/2021] [Indexed: 12/09/2022]

Ooba N, Takahashi Y, Nagamura M, Takahashi M, Ushida M, Kawakami E, Kimura M, Sato T, Tokuyoshi J, Miyazaki C, Shimada M. Safety of elobixibat and lubiprostone in Japanese patients with chronic constipation: a retrospective cohort study. Expert Opin Drug Saf 2021;20:1553-1558. [PMID: 34281471 DOI: 10.1080/14740338.2021.1952980] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]

Sharma A, Rao SSC, Kearns K, Orleck KD, Waldman SA. Review article: diagnosis, management and patient perspectives of the spectrum of constipation disorders. Aliment Pharmacol Ther 2021;53:1250-1267. [PMID: 33909919 PMCID: PMC8252518 DOI: 10.1111/apt.16369] [Citation(s) in RCA: 40] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/08/2020] [Revised: 12/24/2020] [Accepted: 03/31/2021] [Indexed: 12/13/2022]

Pannemans J, Masuy I, Tack J. Functional Constipation: Individualising Assessment and Treatment. Drugs 2021;80:947-963. [PMID: 32451924 DOI: 10.1007/s40265-020-01305-z] [Citation(s) in RCA: 16] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]

Saveleva EE, Tyutrina ES, Nakanishi T, Tamai I, Salmina AB. Inhibitors of the Apical Sodium-Dependent Bile Acid Transporter (ASBT) as Promising Drugs. BIOCHEMISTRY (MOSCOW), SUPPLEMENT SERIES B: BIOMEDICAL CHEMISTRY 2021;15:16-26. [DOI: 10.1134/s1990750821010078] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/18/2020] [Revised: 05/01/2020] [Accepted: 05/06/2020] [Indexed: 01/06/2025]

Eguchi T, Yoshizaki T, Ikeoka S, Takagi M, Fujinami M, Matsuda T, Yamaguchi T, Nonaka T, Amioka S, Katayama N, Inoue K, Matsumoto M, Momose K, Sako T, Noda M, Morisawa T, Okada A. Real-World Comparison of Elobixibat and Lubiprostone Treatment in Patients with Chronic Constipation: A Propensity Score-Matched Analysis. Dig Dis 2020;39:341-350. [PMID: 33142288 DOI: 10.1159/000512745] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/12/2020] [Accepted: 11/02/2020] [Indexed: 02/02/2023]

Affiliation(s)

Takaaki Eguchi Department of Gastroenterology and Hepatology, Osaka Saiseikai Nakatsu Hospital, Osaka, Japan,
Tetsuya Yoshizaki Department of Gastroenterology and Hepatology, Osaka Saiseikai Nakatsu Hospital, Osaka, Japan
Seitaro Ikeoka Department of Gastroenterology and Hepatology, Osaka Saiseikai Nakatsu Hospital, Osaka, Japan
Megumi Takagi Department of Gastroenterology and Hepatology, Osaka Saiseikai Nakatsu Hospital, Osaka, Japan
Maho Fujinami Department of Gastroenterology and Hepatology, Osaka Saiseikai Nakatsu Hospital, Osaka, Japan
Tatsuya Matsuda Department of Gastroenterology and Hepatology, Osaka Saiseikai Nakatsu Hospital, Osaka, Japan
Tsubasa Yamaguchi Department of Gastroenterology and Hepatology, Osaka Saiseikai Nakatsu Hospital, Osaka, Japan
Takahiro Nonaka Department of Gastroenterology and Hepatology, Osaka Saiseikai Nakatsu Hospital, Osaka, Japan
Shohei Amioka Department of Gastroenterology and Hepatology, Osaka Saiseikai Nakatsu Hospital, Osaka, Japan
Norio Katayama Department of Gastroenterology and Hepatology, Osaka Saiseikai Nakatsu Hospital, Osaka, Japan
Kazuki Inoue Department of Gastroenterology and Hepatology, Osaka Saiseikai Nakatsu Hospital, Osaka, Japan
Masanori Matsumoto Department of Gastroenterology and Hepatology, Osaka Saiseikai Nakatsu Hospital, Osaka, Japan
Kenji Momose Department of Gastroenterology and Hepatology, Osaka Saiseikai Nakatsu Hospital, Osaka, Japan
Tomoya Sako Department of Gastroenterology and Hepatology, Osaka Saiseikai Nakatsu Hospital, Osaka, Japan
Mari Noda Department of Gastroenterology and Hepatology, Osaka Saiseikai Nakatsu Hospital, Osaka, Japan
Toshiyuki Morisawa Department of Gastroenterology and Hepatology, Osaka Saiseikai Nakatsu Hospital, Osaka, Japan
Akihiko Okada Department of Gastroenterology and Hepatology, Osaka Saiseikai Nakatsu Hospital, Osaka, Japan

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Saveleva EE, Tyutrina ES, Nakanishi T, Tamai I, Salmina AB. [The inhibitors of the apical sodium-dependent bile acid transporter (ASBT) as promising drugs]. BIOMEDIT︠S︡INSKAI︠A︡ KHIMII︠A︡ 2020;66:185-195. [PMID: 32588824 DOI: 10.18097/pbmc20206603185] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/23/2022]

Yang N, Dong YQ, Jia GX, Fan SM, Li SZ, Yang SS, Li YB. ASBT(SLC10A2): A promising target for treatment of diseases and drug discovery. Biomed Pharmacother 2020;132:110835. [PMID: 33035828 DOI: 10.1016/j.biopha.2020.110835] [Citation(s) in RCA: 49] [Impact Index Per Article: 9.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/05/2020] [Revised: 09/17/2020] [Accepted: 09/28/2020] [Indexed: 12/14/2022] Open

Misawa N, Higurashi T, Takatsu T, Iwaki M, Kobayashi T, Yoshihara T, Ashikari K, Kessoku T, Fuyuki A, Matsuura T, Ohkubo H, Usuda H, Wada K, Naritaka N, Takei H, Nittono H, Matsumoto M, Honda A, Nakajima A, Camilleri M. The benefit of elobixibat in chronic constipation is associated with faecal deoxycholic acid but not effects of altered microbiota. Aliment Pharmacol Ther 2020;52:821-828. [PMID: 32687674 DOI: 10.1111/apt.15950] [Citation(s) in RCA: 16] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/12/2020] [Revised: 05/11/2020] [Accepted: 06/16/2020] [Indexed: 12/11/2022]

Affiliation(s)

Noboru Misawa Department of Gastroenterology and Hepatology, Yokohama City University School of Medicine, Yokohama, Japan
Takuma Higurashi Department of Gastroenterology and Hepatology, Yokohama City University School of Medicine, Yokohama, Japan
Tomohiro Takatsu Department of Gastroenterology and Hepatology, Yokohama City University School of Medicine, Yokohama, Japan
Michihiro Iwaki Department of Gastroenterology and Hepatology, Yokohama City University School of Medicine, Yokohama, Japan
Takashi Kobayashi Department of Gastroenterology and Hepatology, Yokohama City University School of Medicine, Yokohama, Japan
Tsutomu Yoshihara Department of Gastroenterology and Hepatology, Yokohama City University School of Medicine, Yokohama, Japan
Keiichi Ashikari Department of Gastroenterology and Hepatology, Yokohama City University School of Medicine, Yokohama, Japan
Takaomi Kessoku Department of Gastroenterology and Hepatology, Yokohama City University School of Medicine, Yokohama, Japan
Akiko Fuyuki Department of Gastroenterology and Hepatology, Yokohama City University School of Medicine, Yokohama, Japan
Tetsuya Matsuura Department of Gastroenterology and Hepatology, Yokohama City University School of Medicine, Yokohama, Japan
Hidenori Ohkubo Department of Gastroenterology and Hepatology, Yokohama City University School of Medicine, Yokohama, Japan
Haruki Usuda Department of Pharmacology, Shimane University Faculty of Medicine, Izumo, Japan
Koichiro Wada Department of Pharmacology, Shimane University Faculty of Medicine, Izumo, Japan
Nakayuki Naritaka Junshin Clinic Bile Acid Institute, Tokyo, Japan
Hajime Takei Junshin Clinic Bile Acid Institute, Tokyo, Japan
Hiroshi Nittono Junshin Clinic Bile Acid Institute, Tokyo, Japan
Mitsuharu Matsumoto Dairy Science and Technology Institute, Kyodo Milk Industry Co. Ltd, Tokyo, Japan
Akira Honda Gastroenterology, Tokyo Medical University Ibaraki Medical Center, Inashiki, Japan
Atsushi Nakajima Department of Gastroenterology and Hepatology, Yokohama City University School of Medicine, Yokohama, Japan
Michael Camilleri Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN, USA

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Li M, Wang Q, Li Y, Cao S, Zhang Y, Wang Z, Liu G, Li J, Gu B. Apical sodium-dependent bile acid transporter, drug target for bile acid related diseases and delivery target for prodrugs: Current and future challenges. Pharmacol Ther 2020;212:107539. [PMID: 32201314 DOI: 10.1016/j.pharmthera.2020.107539] [Citation(s) in RCA: 42] [Impact Index Per Article: 8.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/18/2019] [Accepted: 03/11/2020] [Indexed: 02/06/2023]

Mousavi T, Nikfar S, Abdollahi M. An update on efficacy and safety considerations for the latest drugs used to treat irritable bowel syndrome. Expert Opin Drug Metab Toxicol 2020;16:583-604. [PMID: 32380874 DOI: 10.1080/17425255.2020.1767067] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]

Tomie A, Yoshida N, Kugai M, Hirose R, Dohi O, Inoue K, Okuda K, Motoyoshi T, Fukumoto K, Inagaki Y, Yoriki H, Inada Y, Okuda T, Hasegawa D, Ogiso K, Murakami T, Soga K, Rani RA, Yoshida N, Itoh Y. The Efficacy and Safety of Elobixibat for the Elderly with Chronic Constipation: A Multicenter Retrospective Cohort Study. Gastroenterol Res Pract 2020;2020:9656040. [PMID: 32411210 PMCID: PMC7204088 DOI: 10.1155/2020/9656040] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/10/2020] [Revised: 04/01/2020] [Accepted: 04/06/2020] [Indexed: 12/13/2022] Open

Affiliation(s)

Akira Tomie Department of Gastroenterology, Saiseikai Kyoto Hospital, Kyoto, Japan
Naohisa Yoshida Department of Molecular Gastroenterology and Hepatology, Kyoto Prefectural University of Medicine, Graduate School of Medical Science, Kyoto, Japan
Munehiro Kugai Department of Gastroenterology, Akashi City Hospital, Hyogo, Japan
Ryohei Hirose Department of Molecular Gastroenterology and Hepatology, Kyoto Prefectural University of Medicine, Graduate School of Medical Science, Kyoto, Japan
Osamu Dohi Department of Molecular Gastroenterology and Hepatology, Kyoto Prefectural University of Medicine, Graduate School of Medical Science, Kyoto, Japan
Ken Inoue Department of Molecular Gastroenterology and Hepatology, Kyoto Prefectural University of Medicine, Graduate School of Medical Science, Kyoto, Japan
Kotaro Okuda Department of Gastroenterology, Kyoto Kujo Hospital, Kyoto, Japan
Takayuki Motoyoshi Department of Gastroenterology, Kyoto City Hospital, Kyoto, Japan
Kohei Fukumoto Department of Gastroenterology, Nara City Hospital, Nara, Japan
Yoshikazu Inagaki Department of Gastroenterology, Nishijin Hospital, Kyoto, Japan
Hiroyuki Yoriki Department of Gastroenterology, Otsu City Hospital, Shiga, Japan
Yutaka Inada Department of Gastroenterology, Fukuchiyama City Hospital, Kyoto, Japan
Takashi Okuda Department of Gastroenterology, Fukuchiyama City Hospital, Kyoto, Japan
Daisuke Hasegawa Department of Gastroenterology, Ayabe City Hospital, Kyoto, Japan
Kiyoshi Ogiso Department of Gastroenterology, Osaka General Hospital of West Japan Railway Company, Osaka, Japan
Takaaki Murakami Department of Gastroenterology, Japan Community Health Care Organization, Kyoto Kuramaguchi Medical Center, Kyoto, Japan
Koichi Soga Department of Gastroenterology, Omihachiman Community Medical Center, Shiga, Japan
Rafiz Abdul Rani Gastroenterology Unit, Faculty of Medicine, Universiti Teknologi MARA, Selangor, Malaysia
Norimasa Yoshida Department of Gastroenterology, Saiseikai Kyoto Hospital, Kyoto, Japan
Yoshito Itoh Department of Molecular Gastroenterology and Hepatology, Kyoto Prefectural University of Medicine, Graduate School of Medical Science, Kyoto, Japan

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Kamei D, Kamei Y, Nagano M, Mineshima M, Nitta K, Tsuchiya K. Elobixibat alleviates chronic constipation in hemodialysis patients: a questionnaire-based study. BMC Gastroenterol 2020;20:26. [PMID: 32005162 PMCID: PMC6995167 DOI: 10.1186/s12876-020-1179-6] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/02/2019] [Accepted: 01/23/2020] [Indexed: 12/18/2022] Open

Abstract

BACKGROUND

Hemodialysis patients are prone to constipation, which can adversely affect their quality of life (QOL). Elobixibat, a highly selective inhibitor of the ileal bile acid transporter, can increase the bile acid level in the colon and, subsequently, enhance colonic motility and secretion. In hemodialysis patients with chronic constipation, it may have a novel action mechanism. However, the effect of elobixibat on such patients' QOL had not been reported. This study aimed to evaluate the effect of elobixibat on the QOL of hemodialysis patients with chronic constipation.

METHODS

This was a multicenter, observational study that used the Japanese version of the Patient Assessment of Constipation-Quality of Life (PAC-QOL) questionnaire on 27 patients (18 men and nine women, age range 47-90 years), who satisfied the Rome 3 diagnostic criteria for functional constipation and were already taking other drugs for constipation. These patients were administered elobixibat 10 mg/day and were asked to respond to the PAC-QOL questionnaire at baseline and after 4 weeks. Bayesian statistics were used to confirm our results.

RESULTS

The number of spontaneous bowel movements per week increased significantly from 2.6 ± 1.2 to 4.1 ± 2.1 (p < 0.001), and the Bristol Stool Form Scale score significantly improved from 1.9 ± 0.8 to 3.6 ± 0.7 (p < 0.001). The Cronbach's alpha was 0.95, and the Guttman split-half reliability coefficient was 0.90. There were significant decreases in the physical discomfort scores from 1.94 ± 0.79 to 0.97 ± 0.72 (p < 0.001); psychosocial discomfort from 1.16 ± 0.93 to 0.63 ± 0.58 (p < 0.001); worries/ concerns from 1.84 ± 0.73 to 1.27 ± 0.59 (p < 0.001), and satisfaction from 2.79 ± 0.61 to 1.98 ± 0.77 (p < 0.001). The total PAC-QOL score significantly decreased from 1.83 ± 0.79 to 1.17 ± 0.56 (p < 0.001). Bayesian statistics confirmed the results' significance.

CONCLUSIONS

Elobixibat reduced the PAC-QOL scores for hemodialysis patients with chronic constipation and improved the patients' QOL. It may serve as a new option for treating constipation in hemodialysis patients.

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Luthra P, Camilleri M, Burr NE, Quigley EMM, Black CJ, Ford AC. Efficacy of drugs in chronic idiopathic constipation: a systematic review and network meta-analysis. Lancet Gastroenterol Hepatol 2019;4:831-844. [DOI: 10.1016/s2468-1253(19)30246-8] [Citation(s) in RCA: 79] [Impact Index Per Article: 13.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/14/2019] [Revised: 06/30/2019] [Accepted: 07/02/2019] [Indexed: 12/13/2022]

Camilleri M. What's in the pipeline for lower functional gastrointestinal disorders in the next 5 years? Am J Physiol Gastrointest Liver Physiol 2019;317:G640-G650. [PMID: 31460793 PMCID: PMC6879894 DOI: 10.1152/ajpgi.00205.2019] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/18/2019] [Revised: 08/13/2019] [Accepted: 08/21/2019] [Indexed: 01/31/2023]

Nakajima A, Taniguchi S, Kurosu S, Gillberg P, Mattsson JP, Camilleri M. Efficacy, long-term safety, and impact on quality of life of elobixibat in more severe constipation: Post hoc analyses of two phase 3 trials in Japan. Neurogastroenterol Motil 2019;31:e13571. [PMID: 30793431 PMCID: PMC6519041 DOI: 10.1111/nmo.13571] [Citation(s) in RCA: 22] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/19/2018] [Revised: 01/07/2019] [Accepted: 01/22/2019] [Indexed: 12/20/2022]

Bouchoucha M, Fysekidis M, Rompteaux P, Airinei G, Sabate JM, Benamouzig R. Influence of Age and Body Mass Index on Total and Segmental Colonic Transit Times in Constipated Subjects. J Neurogastroenterol Motil 2019;25:258-266. [PMID: 30982242 PMCID: PMC6474702 DOI: 10.5056/jnm18167] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/02/2018] [Revised: 12/04/2018] [Accepted: 03/13/2019] [Indexed: 12/12/2022] Open

Ikeda N, Taniguchi S, Seki M. [Pharmacological characteristics and clinical study results of ileal bile acid transporter inhibitor elobixibat (GOOFICE^® tablet 5 mg)]. Nihon Yakurigaku Zasshi 2019;153:129-138. [PMID: 30867382 DOI: 10.1254/fpj.153.129] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/27/2022]

Nakajima A, Shinbo K, Oota A, Kinoshita Y. Polyethylene glycol 3350 plus electrolytes for chronic constipation: a 2-week, randomized, double-blind, placebo-controlled study with a 52-week open-label extension. J Gastroenterol 2019;54:792-803. [PMID: 31011797 PMCID: PMC6698298 DOI: 10.1007/s00535-019-01581-x] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/27/2019] [Accepted: 04/08/2019] [Indexed: 02/04/2023]

Taniguchi S, Yano T, Imaizumi M, Manabe N. Elobixibat, an ileal bile acid transporter inhibitor, induces giant migrating contractions during natural defecation in conscious dogs. Neurogastroenterol Motil 2018;30:e13448. [PMID: 30129138 DOI: 10.1111/nmo.13448] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/14/2018] [Revised: 07/18/2018] [Accepted: 07/18/2018] [Indexed: 12/12/2022]

Murata M, Sugimoto M, Otsuka T, Nishida A, Inatomi O, Bamba S, Andoh A. Successful Helicobacter pylori eradication therapy improves symptoms of chronic constipation. Helicobacter 2018;23:e12543. [PMID: 30324767 DOI: 10.1111/hel.12543] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/06/2018] [Revised: 08/26/2018] [Accepted: 09/04/2018] [Indexed: 12/19/2022]

Abstract

BACKGROUNDS AND AIMS

Constipation is one of the most common gastrointestinal functional disorders. Recently, the gut microbiota has been implicated in the development of constipation. Helicobacter pylori infection is considered to be a possible factor influencing the gut microbiota profile. Here, we investigated the effect of H. pylori eradication therapy on symptoms of chronic constipation.

METHODS

We recruited 166 H pylori-positive patients who underwent eradication therapy after endoscopy. We evaluated the severity of symptoms of chronic constipation before eradication therapy and 2 months post-therapy using two questionnaires, the Gastrointestinal Symptom Rating Scale (GSRS) and the Izumo scale. In addition, we evaluated association with constipation and H. pylori infection in patients with constipation-related symptoms in not only all patients, but also patients with the constipation-related symptoms in relation to eradication outcome, the severity of constipation-related symptoms, and the severity of endoscopic gastric mucosal atrophy.

RESULTS

Mean GSRS scores were 5.10 ± 2.67 in all patients and 6.15 ± 2.91 in constipation patients which were significantly lower than that before eradication (5.78 ± 3.27, P < 0.01 and 8.19 ± 3.09, P < 0.01, respectively). Constipation-related scores of the GSRS questionnaire in the successful eradication group were significantly improved after eradication from 5.63 ± 3.06 in all patients and 8.00 ± 2.85 in constipation patients to 5.11 ± 2.71 (P = 0.02) and 6.16 ± 2.96 (P < 0.01), while scores in the failed eradication group before and after eradication were similar. Constipation-related scores in patients with mild gastric atrophy (Kimura-Takemoto classification, C-I to O-I) were significantly decreased after eradication, but were not decreased in patients with severe atrophy (O-II and O-III).

CONCLUSIONS

Successful eradication therapy for H. pylori infection may confer additional benefits in H. pylori-positive patients with symptoms of chronic constipation, especially in patients with mild gastric atrophy.

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Parkinson's Disease and Current Treatments for Its Gastrointestinal Neurogastromotility Effects. ACTA ACUST UNITED AC 2018;16:489-510. [PMID: 30361854 DOI: 10.1007/s11938-018-0201-3] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]

Simrén M, Tack J. New treatments and therapeutic targets for IBS and other functional bowel disorders. Nat Rev Gastroenterol Hepatol 2018;15:589-605. [PMID: 29930260 DOI: 10.1038/s41575-018-0034-5] [Citation(s) in RCA: 90] [Impact Index Per Article: 12.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]

Chedid V, Vijayvargiya P, Camilleri M. Elobixibat for the treatment of constipation. Expert Rev Gastroenterol Hepatol 2018;12:951-960. [PMID: 30204504 PMCID: PMC6386599 DOI: 10.1080/17474124.2018.1522248] [Citation(s) in RCA: 31] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]

Al-Dury S, Marschall HU. Ileal Bile Acid Transporter Inhibition for the Treatment of Chronic Constipation, Cholestatic Pruritus, and NASH. Front Pharmacol 2018;9:931. [PMID: 30186169 PMCID: PMC6111463 DOI: 10.3389/fphar.2018.00931] [Citation(s) in RCA: 71] [Impact Index Per Article: 10.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/20/2018] [Accepted: 07/30/2018] [Indexed: 12/12/2022] Open

Safety and efficacy of elobixibat for chronic constipation: results from a randomised, double-blind, placebo-controlled, phase 3 trial and an open-label, single-arm, phase 3 trial. Lancet Gastroenterol Hepatol 2018;3:537-547. [PMID: 29805116 DOI: 10.1016/s2468-1253(18)30123-7] [Citation(s) in RCA: 113] [Impact Index Per Article: 16.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/20/2018] [Revised: 03/30/2018] [Accepted: 04/04/2018] [Indexed: 02/07/2023]

Abstract

BACKGROUND

A subset of patients with constipation has reduced colonic bile acid concentrations, which are associated with slow colonic transit. In a previous study, elobixibat, a locally acting ileal bile acid transporter inhibitor, accelerated colonic transit in Japanese patients with functional constipation. In this study, we aimed to determine the efficacy of elobixibat for short-term treatment of chronic constipation, and safety, patient satisfaction, and quality of life with long-term treatment.

METHODS

We did two phase 3 studies of patients aged 20-80 years in Japan with at least 6 months of chronic constipation, who satisfied Rome III criteria for functional constipation, including fewer than three spontaneous bowel movements per week. The first trial, including patients enrolled at 16 clinics, was a 2-week, randomised, double-blind, placebo-controlled study in which (after a 2-week run-in period) patients were randomly assigned (1:1) to either elobixibat 10 mg/day for 2 weeks or placebo. Randomisation was done with permuted block method (block size six) without stratification. Masking to treatment allocation was achieved with identical appearances of elobixibat and placebo, which were supplied in sealed, opaque containers. Group assignment was concealed from patients, investigators, and analysts. The second trial, including patients enrolled at 34 clinics or hospitals, was an open-label, 1-year study in which all patients received elobixibat; participants could titrate the dose to 5 mg/day or 15 mg/day, or maintain the 10 mg/day dose. In both studies, participants took the study drug as an oral tablet once per day before breakfast. The primary outcome of the 2-week randomised trial was the change from baseline (ie, last week of the 2-week run-in) in the frequency of spontaneous bowel movements during week 1 of treatment. The primary outcome of the 52-week open-label trial was safety (type, severity, and incidence of adverse drug reactions) at all times from treatment initiation. All efficacy analyses were based on the modified intention-to-treat (ITT) population without imputation for any missing data. Safety analyses included all patients who received at least one dose of study drug. These trials are registered with the Japan Pharmaceutical Information Center (numbers JapicCTI-153061 and JapicCTI-153062) and have been completed.

FINDINGS

Between Nov 4, 2015, and June 11, 2016, we assigned 133 patients to treatment in the 2-week randomised trial: 70 to elobixibat (69 included in the modified ITT and safety populations) and 63 to placebo. The frequency of spontaneous bowel movements per week during week 1 of treatment was greater with elobixibat (least-squares mean 6·4, 95% CI 5·3-7·6) than with placebo (1·7, 1·2-2·2), p<0·0001). Between Oct 31, 2015, and March 15, 2017, we allocated 341 patients to 52 weeks of elobixibat (340 included in the modified ITT and safety populations). 163 (48%) patients in the 52-week trial had an adverse drug reaction, the most common of which were mild gastrointestinal disorders (in 135 [40%] patients). Inguinal hernia was reported in one patient with elobixibat in the 52-week study as a moderate adverse drug reaction. The most common adverse drug reactions in both trials were mild abdominal pain (13 [19%] patients with elobixibat and one [2%] with placebo in the 2-week randomised trial, and 82 [24%] patients in the 52-week trial) and diarrhoea (nine [13%] patients with elobixibat and none with placebo in the 2-week randomised trial and 50 [15%] in the 52-week trial).

INTERPRETATION

Elobixibat resolved constipation in the short-term, and was well tolerated with both short-term and long-term treatment. The evidence supports the use of this novel approach to increase intracolonic concentrations of endogenous bile acid for the treatment of chronic constipation.

FUNDING

EA Pharma and Mochida Pharmaceutical.

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Al-Dury S, Wahlström A, Wahlin S, Langedijk J, Elferink RO, Ståhlman M, Marschall HU. Pilot study with IBAT inhibitor A4250 for the treatment of cholestatic pruritus in primary biliary cholangitis. Sci Rep 2018;8:6658. [PMID: 29704003 PMCID: PMC5923243 DOI: 10.1038/s41598-018-25214-0] [Citation(s) in RCA: 67] [Impact Index Per Article: 9.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/21/2018] [Accepted: 04/17/2018] [Indexed: 12/31/2022] Open

Malhi H, Camilleri M. Modulating bile acid pathways and TGR5 receptors for treating liver and GI diseases. Curr Opin Pharmacol 2017;37:80-86. [PMID: 29102744 DOI: 10.1016/j.coph.2017.09.008] [Citation(s) in RCA: 34] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/14/2017] [Revised: 09/19/2017] [Accepted: 09/20/2017] [Indexed: 12/27/2022]