Pharmacokinetics and Bioequivalence of Two Formulations of Omeprazole and Sodiun bicarbonate powder, for suspension: A Randomized, Single-Dose, Two-Period, Two-Sequence Crossover Study in Healthy Chinese Volunteers

Introduction: Omeprazole and sodium bicarbonate powder can effectively treatment for acid-related disorders. This study compared the bioequivalence of the two formulations of omeprazole and sodium bicarbonate powder and assessed how CYP2C19 gene polymorphisms affects pharmacokinetic (PK). Methods: This study used a single-center, randomized, single-dose, 2-sequence, and 2-period crossover method, researched among forty healthy Chinese subjects. Blood sample were collected after a single-dose for PK (AUC0-∞, AUC0-t, and Cmax) analysis. The concentrations of Omeprazole in human plasma were determined by HPLC-MS/MS. Finally, the gene polymorphisms of CYP2C19 were assessed by Sanger sequencing. Results: The geometric mean ratios (90% confidence interval) [GMR (95%CI)] of Test/Reference preparation for Cmax: 95.2% (88.48%, 102.43%), AUC0-t: 97.47% (94.4%,101.02%), AUC0-∞:97.68% (94.27%, 101.21%) were within the range of 80.00%-125.00%. Non-parametric test showed no statistical difference in Tmax between the two groups. (P>0.05). All drugs were well tolerated and no severe adverse reactions occurred, and there was also no significant differences in adverse events between the two drugs.For CYP2C19 gene polymorphisms, the results showed that of 40 subjects, 12 subjects were extensive metabolizer (EM), 24 were intermediate metabolizer (IM) and 4 were poor metabolizer (PM). The results of PK parameters showed that different genotypes of CYP2C19 lead to significant differences in t 1/2 , AUC 0-t , AUC 0-∞ and C max , but no significant differences in T max in each group. Conclusion: This study has shown that the pharmacokinetic parameters of the two formulations are not significantly different, which showed bioequivalence and good safety. CYP2C19 gene polymorphism has significant difference in PK parameters of omeprazole sodium bicarbonate suspension. It is suggested that attention should be paid to patients with poor metabolism in clinical application, and timely adjustment of drug delivery regimen should be made to avoid adverse reactions.