M Vaz-da-Silva1, D Hainzl1, L Almeida2, A Dolgner1, P Silveira1, J Maia1, P Soares-da-Silva1. 1. Department of Research & Development, Laboratorios Bial, Human Pharmacology Unit and Laboratory of Pharmacological Research, 4745-457, S. Mamede do Coronado, Portugal. 2. Department of Research & Development, Laboratorios Bial, Human Pharmacology Unit and Laboratory of Pharmacological Research, 4745-457, S. Mamede do Coronado, Portugal. luis.almeida@bial.com.
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 (AUC0-∞) 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 (Cmax) 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 AUC0-∞ as well as for Cmax. 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.
RCT Entities:
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 (AUC0-∞) 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 (Cmax) 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 AUC0-∞ as well as for Cmax. 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.
Authors: V W Steinijans; R Sauter; D Hauschke; E Diletti; R Schall; H G Luus; M Elze; H Blume; C Hoffmann; G Franke Journal: Int J Clin Pharmacol Ther Date: 1995-08 Impact factor: 1.366
Authors: P J Prichard; N D Yeomans; G W Mihaly; D B Jones; P J Buckle; R A Smallwood; W J Louis Journal: Gastroenterology Date: 1985-01 Impact factor: 22.682
Authors: Manuel Vaz-da-Silva; Ana I Loureiro; Teresa Nunes; Joana Maia; Susana Tavares; Amilcar Falcão; Pedro Silveira; Luis Almeida; Patricio Soares-da-Silva Journal: Clin Drug Investig Date: 2005 Impact factor: 2.859