Bioavailability and Bioequivalence of Two Enteric-Coated Formulations of Omeprazole in Fasting and Fed Conditions
- 215 Downloads
Objective: To investigate the relative bioavailability and bioequivalence, in fasting and fed conditions, of repeated doses of two omeprazole enteric-coated formulations in healthy volunteers.
Material and methods: Open label, single-centre study consisting of two consecutive randomised, two-way crossover trials (a fasting trial and a fed trial). Each trial consisted of two 7-day treatment periods in which subjects received one daily dose of the test (Ompranyt®) or reference (Mopral®) formulations. At day 7 and day 14 (fasting trial), products were administered in fasting conditions and blood samples were taken for omeprazole plasma assay over 12 hours. At day 21 and day 28 (fed trial), products were administered after a standard high-calorie and high-fat meal and 12-hour blood samples taken. Omeprazole plasma concentrations were quantified by a validated method using a reverse-phase high performance liquid chromatography with UV detection (HPLC-UV).
Results: Twenty-four subjects were enrolled and 23 completed the study. Under fasting conditions, the mean ± SD maximum omeprazole plasma concentration (Cmax) was 797 ± 471 μg/L for Ompranyt® and 747 ± 313 μg/L for Mopral® with a point estimate (PE) of 1.01 and a 90% confidence interval (CI) of 0.88, 1.16. The mean ± SD area under the plasma concentration curve from administration to last observed concentration (AUC0–12) was 1932 ± 1611 μg · h/L and 1765 ± 1327 μg · h/L for Ompranyt® and Mopral®, respectively (PE = 1.09; 90% CI 0.95, 1.25). In the presence of food, the Cmax was 331 ± 227 μg/L and 275 ± 162 μg/L (PE = 1.21; 90% CI 0.92, 1.59) and AUC0–12 was 1250 ± 966 μg · h/L and 1087 ± 861 μg · h/L (PE = 1.16; 90% CI 0.92, 1.47) for Ompranyt® and Mopral®, respectively. Bioequivalence of the formulations in the fasting condition was demonstrated both for AUC0–12 and for Cmax because the 90% CI lay within the acceptance range of 0.80–1.25. In contrast with the fasting condition, there were significant reductions in rate (Cmax) and extent (AUC0–12) of systemic exposure when test and reference formulations were administered with food. The food effect was more marked with Mopral® than with Ompranyt®, and the bioequivalence criterion was not fulfilled because the 90% CI fell out of the acceptance range of 0.80, 1.25, for both Cmax and AUC0–12. The two formulations were similarly well tolerated.
Conclusion: Bioequivalence of Ompranyt® (test formulation) and Mopral® (reference) formulations was demonstrated after repeated dosing in the fasting condition. Following a high-calorie and high-fat meal, there was a significant reduction in rate and extent of systemic exposure for both products, with Ompranyt® being less affected than Mopral® by the presence of food.
KeywordsOmeprazole Fasting Condition Study Product Bioequivalence Study Reference Formulation
This work was financially supported by BIAL SA. All the authors are employees of BIAL SA.
- 3.Guidance for Industry (Draft). Bioavailability and bioequivalence studies for orally administered drug products: general considerations. Rockville, MD: US Department of Health and Human Services, Food and Drug Administration Center for Drug Evaluation and Research (CDER), 2002 JulGoogle Scholar
- 4.Guidance for Industry (Draft). Food-effect bioavailability and fed bioequivalence studies: study design, data analysis, and labeling. Rockville, MD: US Department of Health and Human Services, Food and Drug Administration Center for Drug Evaluation and Research (CDER), 2001 OctGoogle Scholar
- 5.Note for guidance on modified release oral and transdermal dosage forms. European Agency for the Evaluation of Medicinal Products, Committee for Proprietary Medicinal Products, CPMP/EWP/280/96 (Draft 15), London, 1999 Jul 28Google Scholar
- 8.Note for guidance on the investigation of bioavailability and bioequivalence. London: European Agency for the Evaluation of Medicinal Products, Committee for Proprietary Medicinal Products, CPMP/EWP/QWP/1401/98, 2001 Jul 26Google Scholar
- 9.Critérios Exigibles a los genéricos de Omeprazol. Comité de Evaluación de Medicamentos de Uso Humano (CODEM), Agencia Española del Medicamento, 2000 Feb 11Google Scholar
- 16.Guidance for Industry. Statistical approaches to establishing bioequivalence. Rockville, MD: US Department of Health and Human Services, Food and Drug Administration Center for Drug Evaluation and Research (CDER), 2001 JanGoogle Scholar
- 17.USP DI. Drug information to the health care professional, 22nd ed. Omeprazole Systemic. Greenwood Village (CO): Micromedex, 2002: 2210-2213Google Scholar
- 19.Physicians’ Desk Reference, 57th ed. Prilosec. Montvale: Thomson PDR, 2003: 627–632Google Scholar
- 20.Rhoss K, Andren K, Heggelund A, et al. Bioavailability of omeprazole given in conjunction with food. III World Congr Clin Pharmacol Ther, Stockholm July–Aug 1986 [abstract]. Acta PharmacolToxicol 1986; 85Suppl. 5: 207Google Scholar