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

BACKGROUND: The pharmacokinetics and bioequivalence of esomeprazole in healthy Chinese subjects and the effects of food on the pharmacokinetics have not been well studied. AIM: To evaluate the pharmacokinetic characteristics of esomeprazole magnesium (Eso) enteric- coated capsule in the healthy subjects in China and the bioequivalence of the two formulations. METHODS: This 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 C(max), area under the curve (AUC)(0-t), and AUC(0-inf) were calculated to evaluate the bioequivalence. RESULTS: Pharmacokinetic parameters were evaluated after subjects took the test formulation and control formulation under fasting status. The ratio of geometric means of C(max) was 104.15%, with a confidence interval (CI) of 98.20-110.46%. The ratio of geometric means of AUC(0-t) was 105.26%, with a CI of 99.80-111.01%. The ratio of geometric means of AUC(0-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 C(max )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 AUC(0-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 AUC(0-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. CONCLUSION: The two types of esomeprazole tablets were bioequivalent under both fasting and fed states, and both were generally well tolerated.