Relative Bioavailability of Two Enteric-Coated Formulations of Omeprazole following Repeated Doses in Healthy Volunteers

Abstract

Objective

This study aimed to investigate the relative bioavailability and bioequivalence of two omeprazole enteric-coated formulations following repeated doses (steady state) in healthy male and female adult volunteers.

Design and Study Participants

The study formulation (Ompranyt® 20mg capsules, Bial-Industrial Farmaceutica SA, Spain) was compared with an omeprazole reference formulation (Mopral® 20mg capsules, Laboratório Astra, Spain). 24 participants were randomised using a two-way, crossover design to receive either one capsule/day of Ompranyt® or one capsule/day of Mopral® during two sequential periods of five consecutive days each. The participants were administered the drugs in the fasting state. Omeprazole concentrations in plasma samples were quantified by a validated method using a reversed-phase high performance liquid chromatography with UV detection (HPLC-UV). The validation method is described.

Setting

The study was conducted at the Human Pharmacology Unit, Department of Research & Development, Laboratorios Bial (S. Mamede do Coronado, Portugal).

Results

The arithmetic mean ± SD values of the area under the plasma concentration versus time curve from time zero to infinity (AUC_0-∞) were 1474 ± 1417 μg/L·h for Ompranyt® and 1490 ± 1276 μg/L·h for Mopral®. The geometric means ratio (Ompranyt®/Mopral®) was 0.99, with 90% confidence intervals (CI) of 0.97–1.03. The estimated maximum plasma concentration (C_max) was 630.1 ± 516.7 μg/L for Ompranyt® and 736.7 ± 443.3 μg/L for Mopral®, with a geometric means ratio (Ompranyt®/Mopral®) of 0.96 (90% CI: 0.94-0.99). Bioequivalence of these two formulations was accepted based on the two one-sided ANOVA for AUC_0-∞ as well as for C_max. In both cases, the 90% CI lies within the acceptance range of 0.80–1.25.

Conclusion

Bioequivalence of Ompranyt® and Mopral® was demonstrated after repeated drug administration in fasting conditions, and both products were similarly well tolerated. Therefore, both formulations are expected to be equivalent in a clinical setting.