Bioequivalence of two esomeprazole magnesium enteric-coated formulations in healthy Chinese subjects.

Abstract

BACKGROUNDThe pharmacokinetics and bioequivalence of esomeprazole in healthy Chinese subjects and the effects of food on the pharmacokinetics have not been well studied.AIMTo evaluate the pharmacokinetic characteristics of esomeprazole magnesium (Eso) enteric- coated capsule in the healthy subjects in China and the bioequivalence of the two formulations.METHODSThis study was conducted in the Phase I Clinical Trial Unit of the Affiliated Hospital of Changchun University of Chinese Medicine. A total of 64 healthy subjects were enrolled in the study. Thirty-two subjects fasted or fed, took the test or reference formulation Eso enteric-coated capsule by a four-cycle, two-sequence crossover of fasting/fed, self-controlled method. The liquid chromatography-mass spectrometry was performed to determine the drug plasma concentration at 16 different time points within 12 h after drug administration. The pharmacokinetic parameters Cmax, area under the curve (AUC)0-t, and AUC0-inf were calculated to evaluate the bioequivalence.RESULTSPharmacokinetic parameters were evaluated after subjects took the test formulation and control formulation under fasting status. The ratio of geometric means of Cmax was 104.15%, with a confidence interval (CI) of 98.20-110.46%. The ratio of geometric means of AUC0-t was 105.26%, with a CI of 99.80-111.01%. The ratio of geometric means of AUC0-inf was 105.37%, with a CI of 99.97-111.06%. The pharmacokinetic parameters were also evaluated after subjects took the reference formulation of Eso enteric-coated capsule after eating. The upper limit of 95% CI of the geometric mean ratio of pharmacokinetic parameters of Eso enteric-coated capsules in the postprandial state Cmax was -0.1689, and the point estimate was 0.9509 (0.80-1.25). The upper limit of 95% CI of the geometric mean ratio of pharmacokinetic parameters of Eso enteric-coated capsules in the postprandial state AUC0-t was -0.1015 (≤ 0) , and the point estimate was 0.9003 (0.80-1.25). The upper limit of 95% CI of the geometric mean ratio of pharmacokinetic parameters of Eso enteric-coated capsules in the postprandial state AUC0-inf was -0.0593 (≤ 0), and the point estimate was 0.8453 (0.80-1.25). The results indicated that the two formulations were bioequivalent under both fasting and fed states.CONCLUSIONThe two types of esomeprazole tablets were bioequivalent under both fasting and fed states, and both were generally well tolerated.