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((R))) or reference (Mopral((R))) 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 (C(max)) was 797 +/- 471 mug/L for Ompranyt((R)) and 747 +/- 313 mug/L for Mopral((R)) 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 (AUC(0-12)) was 1932 +/- 1611 mug . h/L and 1765 +/- 1327 mug . h/L for Ompranyt((R)) and Mopral((R)), respectively (PE = 1.09; 90% CI 0.95, 1.25). In the presence of food, the C(max) was 331 +/- 227 mug/L and 275 +/- 162 mug/L (PE = 1.21; 90% CI 0.92, 1.59) and AUC(0-12) was 1250 +/- 966 mug . h/L and 1087 +/- 861 mug . h/L (PE = 1.16; 90% CI 0.92, 1.47) for Ompranyt((R)) and Mopral((R)), respectively. Bioequivalence of the formulations in the fasting condition was demonstrated both for AUC(0-12) and for C(max) 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 (C(max)) and extent (AUC(0-12)) of systemic exposure when test and reference formulations were administered with food. The food effect was more marked with Mopral((R)) than with Ompranyt((R)), and the bioequivalence criterion was not fulfilled because the 90% CI fell out of the acceptance range of 0.80, 1.25, for both C(max) and AUC(0-12). The two formulations were similarly well tolerated. CONCLUSION: Bioequivalence of Ompranyt((R)) (test formulation) and Mopral((R)) (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((R)) being less affected than Mopral((R)) by the presence of food.
RCT Entities:
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((R))) or reference (Mopral((R))) 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 (C(max)) was 797 +/- 471 mug/L for Ompranyt((R)) and 747 +/- 313 mug/L for Mopral((R)) 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 (AUC(0-12)) was 1932 +/- 1611 mug . h/L and 1765 +/- 1327 mug . h/L for Ompranyt((R)) and Mopral((R)), respectively (PE = 1.09; 90% CI 0.95, 1.25). In the presence of food, the C(max) was 331 +/- 227 mug/L and 275 +/- 162 mug/L (PE = 1.21; 90% CI 0.92, 1.59) and AUC(0-12) was 1250 +/- 966 mug . h/L and 1087 +/- 861 mug . h/L (PE = 1.16; 90% CI 0.92, 1.47) for Ompranyt((R)) and Mopral((R)), respectively. Bioequivalence of the formulations in the fasting condition was demonstrated both for AUC(0-12) and for C(max) 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 (C(max)) and extent (AUC(0-12)) of systemic exposure when test and reference formulations were administered with food. The food effect was more marked with Mopral((R)) than with Ompranyt((R)), and the bioequivalence criterion was not fulfilled because the 90% CI fell out of the acceptance range of 0.80, 1.25, for both C(max) and AUC(0-12). The two formulations were similarly well tolerated. CONCLUSION: Bioequivalence of Ompranyt((R)) (test formulation) and Mopral((R)) (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((R)) being less affected than Mopral((R)) by the presence of food.
Authors: M Vaz-da-Silva; D Hainzl; L Almeida; A Dolgner; P Silveira; J Maia; P Soares-da-Silva Journal: Clin Drug Investig Date: 2001-03 Impact factor: 2.859