Bioequivalence Study of Two Loperamide Hydrochloride 2 mg Formulations: An Open-Label, Randomized, Single-Dose, Two-Way Crossover Study in Healthy Volunteers under Fasting Conditions

Abstract

The objective of this study was to compare the rate and extent of drug absorption of the test product (Colodium 2 mg Capsule, Hovid Bhd.) against the reference product (Imodium® 2 mg Capsule, Janssen Cilag S.A.) in twentythree healthy male volunteers under fasting condition in order to evaluate bioequivalence. A single dose of 8 mg (4 capsules of 2 mg each) of test and reference products were given to volunteers during two periods of the study respectively. There was a 7 day washout period between the two study periods. Blood samples were taken at pre-dose and at 13 time points up till 48 h post dosing. Plasma levels of loperamide were determined by liquid chromatography-tandem mass spectrometry. The plasma concentration-time data was used to estimate the pharmacokinetic parameters, namely, Cmax, Tmax, AUC0-t and AUC0-∞. Analysis of variance (ANOVA) procedure was used to analyze the values of Cmax, AUC0-t, AUC0-∞ and ke obtained from the two preparations. For the analysis of Tmax values, the Wilcoxon Signed Rank Test for paired samples was used. In this study, the 90% confidence interval for the ratio of the AUC0-t, AUC0-∞ and Cmax were calculated to be between 0.8730-1.0181, 0.8852-0.9891 and 0.8023- 0.9559 respectively. All of the values were within the acceptable bioequivalence requirement of 0.8000-1.2500. No drug-related adverse event was reported throughout the study. Thus, the two preparations could be concluded to be bioequivalent and interchangeable.