Brief Article
Copyright ©2010 Baishideng Publishing Group Co., Limited. All rights reserved.
World J Gastrointest Pharmacol Ther. Oct 6, 2010; 1(5): 112-118
Published online Oct 6, 2010. doi: 10.4292/wjgpt.v1.i5.112
An open-label, randomized, cross-over bioequivalence study of lafutidine 10 mg under fasting condition
Bhupesh Dewan, Raghuram Chimata
Bhupesh Dewan, Director Medical Services, Zuventus Healthcare Ltd., Mumbai 400072, India
Raghuram Chimata, Clinical Research Associate, Zuventus Healthcare Ltd., Mumbai 400072, India
Author contributions: Dewan B was involved in the conceptualization of the study, designing of the protocol, initiation, supervision, auditing of the sites, interpretation of the data and statistical outcomes and revision of the manuscript drafts; Chimata R was involved in monitoring of the study, statistical analysis and interpretation of the data and the compilation of the manuscript draft; all the authors read and approved the final version of the manuscript.
Correspondence to: Dr. Bhupesh Dewan, MBBS, MD, Director Medical Services, Zuventus Healthcare Ltd., 5119 ‘D’ Wing, Oberoi Garden Estate, Chandivilli, Mumbai 400 072, India.
Telephone: +91-22-28472823 Fax: +91-22-28472828
Received: April 23, 2010
Revised: September 21, 2010
Accepted: September 28, 2010
Published online: October 6, 2010

AIM: To assess the relative bioavailability and pharmacokinetic properties of two formulations (test and reference) of Lafutidine 10 mg.

METHODS: The study was performed as an open label, randomized, two-way, two-period, two-treatment, single dose cross-over bioequivalence study, under non-fed condition to compare the pharmacokinetic profiles of the lafutidine formulation manufactured by Emcure Pharmaceuticals Ltd., India using an indigenously developed active pharmaceutical ingredient (API) and the commercially available Stogra® formulation, of UCB Japan Co., Ltd., Japan. The two treatments were separated by a wash-out period of 5 d. After an overnight fasting period of 10 h, the subjects were administered either the test or the reference medication as per the randomization schedule. Blood samples were collected at intervals up to 24 h, as per the approved protocol. Concentrations of lafutidine in plasma were analyzed by a validated liquid chromatography/tandem mass spectrometry (LC/MS/MS) method, and a non-compartmental model was used for pharmacokinetic analysis. The pharmacokinetic parameters were subjected to a 4-way ANOVA accounting for sequence, subjects, period and treatment. Statistical significance was evaluated at 95% confidence level (P ≥ 0.05).

RESULTS: The mean (± SD) values of the pharmacokinetic parameters (test vs reference) were Cmax (265.15 ± 49.84 ng/mL vs 246.79 ± 29.30 ng/mL, P < 0.05), Area under the curve (AUC)(0-t) (1033.13 ± 298.74 ng.h/mL vs 952.93 ± 244.07 ng.h/mL, P < 0.05), AUC(0-∞) (1047.61 ± 301.22 ng.h/mL vs 964.21 ± 246.45 ng.h/mL, P < 0.05), and t½(1.92 ± 0.94 h vs 2.05 ± 1.01 h, P < 0.05). The 90% confidence intervals (CI) for the test/reference ratio of mean Cmax, AUC(0-t), and AUC(0-∞) were within the acceptable range of 80.00 to 125.00. The mean times (± SD) to attain maximal plasma concentration (tmax) of lafutidine were 0.95 ± 0.24 h vs 1.01 ± 0.29 h (P < 0.05) for the test and the reference formulations respectively. Both the formulations were well tolerated.

CONCLUSION: In summary, this study has demonstrated the bioequivalence of the two formulations of lafutidine 10 mg. Hence it can be concluded that the two formulations can be used interchangeably in clinical settings.

Keywords: Liquid chromatography/tandem mass spectrometry, Lafutidine, Gastroprotective, Pharmacokinetics, Bioequivalence