血浆中雷尼替丁和铋的药动学和生物等效性研究

目的建立高效液相色谱(HPLC)和电感耦合等离子体-质谱(ICP-MS)分别测定人血浆中雷尼替丁和铋质量浓度的方法 ,并应用该法进行雷尼替丁和铋在健康人体内的药动学特征研究和复方盐酸雷尼替丁片生物等效性评价。方法采用HPLC法和ICP-MS技术,分别测定20名健康男性受试者经口给予复方盐酸雷尼替丁片和复方雷尼替丁胶囊后不同时刻血浆中雷尼替丁和铋的质量浓度,分别绘制血药质量浓度-时间曲线,并计算主要药动学参数。结果受试制剂和参比制剂中雷尼替丁的主要药动学参数如下:tmax分别为(1.9±0.5)和(2.1±0.6)h,ρmax分别为(492.8±276.7)和(466.5±224.4)μg.L-1,t1/2分别为(2.9±1.6)和(2.8±1.0)h,用梯形法计算,AUC0-t分别为(2 548.3±895.6)和(2 377.5±887.0)μg.h.L-1,AUC0-∞分别为(2 562.9±912.8)和(2 377.5±887.0)μg.h.L-1,雷尼替丁的相对生物利用度平均为(111.6±35.4)%。受试制剂和参比制剂中铋的主要药动学参数如下:tmax分别为(0.4±0.2)和(0.3±0.1)h,ρmax分别为(56.0±40.2)和(53.3±37.9)μg.L-1,t1/2分别为(6.9±2.6)和(7.2±2.3)h,用梯形法计算,AUC0-t分别为(151.8±118.9)和(156.3±117.9)μg.h.L-1,AUC0-∞分别为(153.1±120.2)和(157.7±119.3)μg.h.L-1,铋的相对生物利用度平均为(95.3±16.2)%。结论复方盐酸雷尼替丁片与复方雷尼替丁胶囊两种制剂具有生物等效性。

Pharmacokinetics and bioequivalence of ranitidine and bismuth in human plasma

Objective To set up the sensitive and rapid HPLC and ICP-MS methods for determination of ranitidine and bismuth respectively in plasma, and study the pharmacokinetics and relative bioequivalence following oral administration of compound ranitidine tablets and compound ranitidine capsules in healthy volunteers. Methods Twenty healthy volunteers took compound ranitidine tablets and compound ranitidine capsules, respectively. The concentration of ranitidine in plasma was determined by HPLC, and the concentration of bismuth in plasma was determined by ICP-MS, then the concentration-time curves were plotted and the main pharmacokinetic parameters were calculated, respectively. Results The main pharmacokinetic parameters of test and reference preparation respectively in plasma were: ranitidine t_max = (1.9 ± 0.5) and (2.1 ± 0.6) h, ρ_max = (492.8 ± 276.7) and (466.5 ± 224.4) μg·L^-1, t _1/2 = (2.9 ± 1.6) and (2.8 ± 1.0) h, AUC _0-t = (2 548.3 ± 895.6) and (2 377.5 ± 887.0) μg·h·L^-1, AUC_0-∞ = (2 562.9 ± 912.8) and (2 377.5 ± 887.0) μg·h·L^-1. The relative bioavailability of tropisetron for test drug was (111.6 ± 35.4)% of ranitidine; bismuth t_max = (0.4 ± 0.2) and (0.3 ± 0.1) h, ρ_max = (56.0 ± 40.2) and (53.3 ± 37.9) μg·L^-1, t _1/2 = (6.9 ± 2.6) and (7.2 ± 2.3) h，AUC _0-t = (151.8 ± 118.9) and (156.3 ± 117.9) μg·h·L^-1, AUC _0-∞ = (153.1 ± 120.2) and (157.7 ± 119.3) μg·h·L^-1. The relative bioavailability of bismuth was (95.3±16.2)%. Conclusion The two kinds of compound ranitidine formulations are bioequivalent in healthy volunteers.