奥美拉唑碳酸氢钠干混悬剂在健康中国人中的药代动力学研究和生物等效性评价

Pharmacokinetics study and bioequivalence evaluation of omeprazole dry suspensions in Chinese healthy subjects

目的研究奥美拉唑碳酸氢钠干混悬剂在健康人体的药代动力学和相对生物利用度,并以原研奥美拉唑碳酸氢钠干混悬剂为参比制剂,进行生物等效性评价。方法用单中心、随机、两周期、两交叉、自身对照试验设计,分别入组40例受试者,Ⅰ组交叉口服受试制剂或参比制剂奥美拉唑碳酸氢钠干混悬剂20 mg,Ⅱ组交叉口服受试制剂或参比制剂奥美拉唑干混悬剂40 mg。用LC-MS/MS法测定血浆中奥美拉唑浓度,用WinNonlin 8.0计算药代动力学参数,并进行两种制剂的生物等效性评价。结果受试者给予受试制剂及参比制剂奥美拉唑碳酸氢钠干混悬剂20 mg后C_(max)分别为(869.85±366.05)和(858.38±370.23)ng·mL^(-1),AUC_(0-t)分别为(1006.33±939.25)和(1022.64±1010.28)h·ng·mL^(-1)。C_(max)和AUC_(0-t)的90%置信区间分别为92.93%~112.62%和95.50%~102.90%。受试者给予受试制剂及参比制剂奥美拉唑碳酸氢钠干混悬剂40 mg后C_(max)分别为(2276.00±787.45)和(2162.92±793.21)ng·mL^(-1),AUC_(0-t)分别为(3937.53±3336.61)和(3929.18±3034.03)h·ng·mL^(-1)。C_(max)和AUC_(0-t)的90%置信区间分别为96.41%~117.74%和95.13%~103.49%。药代动力学参数个体间变异均超过25%。结论受试制剂与参比制剂奥美拉唑碳酸氢钠干混悬剂20 mg和40 mg的药代动力学参数分别在80.00%~125.00%等效区间内,表明在中国健康受试者中具有生物等效性。

Objective To study the pharmacokinetics and relative bioavailability of omeprazole dry suspension in healthy subjects,a study was carried out to evaluate of bioequivalence of the reference omeprazole dry suspension and the test preparation.Methods A single-center,randomized,two-period,two-crossover trial design was carried,and 40 subjects were enrolled in two groups,respectively.Each subject randomly accepted single oral test or reference drug 20 mg/40 mg.The concentration of omeprazole in plasma was determined by LC-MS/MS method,and the pharmacokinetic parameters were calculated and the bioequivalence was evaluated by WinNonlin 8.0 software.Results Pharmacokinetic parameters of test or reference omeprazole sodium bicarbonate dry suspension 20 mg:C_(max) were(869.85±366.05)and(858.38±370.23)ng·mL^(-1),AUC_(0-t) were(1006.33±939.25)and(1022.64±1010.28)h·ng·mL^(-1),respectively.The 90% confidence intervals of C_(max) and AUC_(0-t) were 92.93%-112.62%and 95.50%-102.90%,respectively.Pharmacokinetic parameters of test or reference omeprazole sodium bicarbonate dry suspension 40 mg:C_(max) were(2276.00±787.45)and(2162.92±793.21)ng·mL^(-1),AUC_(0-t) were(3937.53±3336.61)and(3929.18±3034.03)h·ng·mL^(-1),respectively.The 90%confidence intervals of C_(max) and AUC_(0-t) were 96.41%-117.74%,and 95.13%-103.49%,respectively.The inter-individual variation of pharmacokinetic parameters exceeded 25%.Conclusion The pharmacokinetic parameters of omeprazole sodium bicarbonate dry suspension 20 mg and 40 mg test formulations and reference formulations were within the equivalent range of 80.00%-125.00%which indicated that these two formulations of 20 mg and 40 mg were bioequivalent in Chinese healthy subjects.