Bioequivalence Assessment of Two Capsule Formulations of Omeprazole in Healthy Volunteers

Abstract

A randomized, single-dose, crossover study was conducted to assess the bioavailability of two omeprazole (CAS 73590-58-6) capsule formulations, Emilok (test) and a commercially available original preparation (reference), under fasting conditions. A 20 mg dose of each formulation was administered to 36 healthy male volunteers with one-week washout period, 17 blood samples were collected over 12 h, plasma omeprazole concentrations were determined by a locally validated high performance liquid chromatography (HPLC) assay, and omeprazole pharmacokinetic parameters were analyzed by the standard non-compartmental method. Mean +/- SD of Cmax, Tmax, AUC(0 --> t), AUC(0 --> infinity), and t1/2 were 0.41 +/- 0.21 and 0.48 +/- 0.27 microg/ml, 1.98 +/- 1.02 and 1.63 +/- 0.78 h, 0.95 +/- 0.78 and 1.00 +/- 0.90 microg x h/ml, 0.99 +/- 0.81 and 1.04 +/- 0.95 microg x h/ml, and 1.30 +/- 0.64 and 1.14 +/- 0.61 h for the test and reference formulations, respectively. The parametric 90% confidence intervals on mean difference between log-transformed values of the two formulations were within the acceptable bioequivalence range of 80% to 125% for AUC(0 --> t) and AUC(0 --> infinity) (88.63% to 104.98%, and 91.71% to 106.86%, respectively) but not for Cmax (76.27% to 103.63%). ANOVA revealed significant subject's effect for AUC(0 --> t), AUC(0 --> infinity), Cmax, and t1/2 with a ratio of the inter-subject to intra-subject coefficient of variation of 3.66, 3.92, 1.25, and 1.46, respectively. The results confirm the presence of marked individual variations in the pharmacokinetics of omeprazole and indicate that the two formulations are equivalent in relation to the extent but not the rate of absorption.