复方法莫替丁咀嚼片的人体药动学

Pharmacokinetics of compound famotidine chewable tabletsin Chinese healthy volunteers

目的:研究复方法莫替丁咀嚼片人体药动学。方法:12名健康志愿者在空腹及餐后条件下分别单次口服给药。LC/MS/MS方法测定血浆中法莫替丁的浓度,采用DAS ver1.0药动学程序进行数据处理,计算药动学参数。结果:在空腹和餐后条件下,Tmax分别为(1.7±0.4)和(3.2±1.0)h;Cmax分别为(83.9±28.6),(67.6±21.2)μg.L-1;AUC0-14分别为(469.2±141.9),(408.1±116.8)μg.h.L-1;t1/2ka分别为(0.5±0.3),(0.9±0.4)h;t1/2α分别为(2.2±1.6),(1.9±1.9)h;t1/2α分别为(3.8±1.1),(3.8±2.3)h;Vd分别为(3.5±2.2),(3.3±3.7)L;CLp分别为(0.6±0.2),(0.50±0.3)L.h-1。结论:复方法莫替丁咀嚼片中的法莫替丁在人体内的动力学过程符合二房室模型。食物对复方制剂中法莫替丁的药动学特性有一定影响。餐后给药,法莫替丁的吸收速度减慢,吸收程度也有所降低,而其分布、消除基本无变化。

OBJECTIVE To investigate the pharmacokinetics of compound famotidine chewable tablets in Chinese healthy volunteers. METHODS a single 20 mg dose of compound famotidine chewable tablets was oral administered to 12 healthy subjects （6 males and 6 females） in the fasting and fed states. The plasma concentrations of famotidine were determined by a validated LC/MS/MS method. The plasma concentrations-time data were calculated with DAS ver 1.0 program. RESULTS The main pharmacokinetic parameters of famotidine were： Tmax was （1.7 ± 0. 4） and （3. 2 ± 1.0）h, Cmax was （83. 9 ± 28. 6） and （67.6±21.2）μg.L^-1, AUCqH4 was （469.2± 141.9） and （408. 1 ± 116.8）μag .h .L^-1, t1/2ka was （0.5±0.3） and （0.9± 0. 4）h, t,/2, was （2. 2 ± 1.6） and （1.9 ± 1.9）h, t,/2a, was （3.8 ± 1.1） and （3. 8 ± 2. 3）h, Vd was （3.5 ± 2. 2） and （3. 5 ± 3.7）L, CLp was （0. 6 ± 0. 2） and （0. 5 ± 0. 3） L. h^-1. CONCLUSION The plasma concentrations-time curve of famotidine after oral administration of a single 20 mg dose fits to a two-compartment model. The pharrnaeokineties of famotidine are affected by food ingestion. Compared with fasting, orally administering compound famotidine chewable tablets with food could significantly reduce the bioavailability of famotidine, statistically delayed absorption and decrease peak plasma concentrations, at the same time, the distribution and the rate of elimination of famotidine remain unchanged.