目的研究复方法莫替丁咀嚼片在正常人体内的药动学,据此拟定临床给药方案。方法采用HPLC测定12名健康志愿受试者单剂量空腹po(低、中、高剂量,即含法莫替丁20,30,40 mg)、进食后口服以及多剂量口服复方法莫替丁咀嚼片后,法莫替丁血药浓度变化情况。结果单剂量空腹po低、中、高3个剂量法莫替丁AUC_0→12分别是:(243.39±41.10),(347.05±25.95)和(516.12±55.37)μg·h·L^-1;达峰时间分别为:(2.96±0.33),(2.50±0.30)和(2.63±0.38)h;峰浓度分别是:(67.10±5.71),(94.18±3.21)和(125.43±5.30)μg·L^-1;消除速率常数分别为:(0.18±0.02),(0.17±0.02)和(0.19±0.04)h^-1;消除半衰期分别为:(3.85±0.52),(4.12±0.59)和(3.85±0.77)h。进食后服用低剂量的供试制剂,法莫替丁AUC_0→12为(257.94±39.88)μg·h·L^-1,达峰时间为(2.83±0.39)h,峰浓度为(64.56±2.18)μg·L^-1,消除速率常数为(0.20±0.04)h^-1,消除半衰期为(3.54±0.69)h。多剂量给予20 mg供试制剂达稳态后,法莫替丁AUC_0→τ为(310.02±23.95)μg·h·L^-1,达峰时间为(2.46±0.33)h,稳态谷浓度是(7.84±1.31)μg·L^-1,稳态峰浓度为(60.78±2.13)μg·L^-1,平均稳态血药浓度是(25.83±2.00)μg·L^-1,消除速率常数为(0.20±0.03)h^-1,消除半衰期为(3.61±0.54)h,波动度(DF)为2.06,蓄积因子为0.02。结论对空腹 po 3个剂量供试制剂的AUC_0→12/剂量进行q检验,结果表明,法莫替丁在体内符合线性动力学过程;对空腹与进食后给予供试制剂的有关药动学参数进行差别检验,结果表明,食物对法莫替丁的体内过程无显著影响;多剂量试验结果表明,法莫替丁在体内无蓄积作用。

OBJECTIVE To investigate the pharmacokinetics of compound famotidine chewing tablets in healthy volunteers and to establish the clinical prescription.METHODS The plasma concentrations of famotidine for single dosage oral administration without meal(low,middle and high dosage,they contained 20,30 and 40 mg famotidine) and with meal as well as multiple doses were examined.RESULTS The AUC_0→12 of single dosage oral administration were(243.39±41.10),(347.05±25.95) and(516.12±55.37)μg·h·L^-1 respectively,peak time(t_max) were(2.96±0.33),(2.50±0.30) and(2.63±0.38)h,plasma peak concentration(ρ_max) were(67.10±5.71),(94.18±3.21) and(125.43±5.30)μg·L^-1,elimination rate constants(k) were(0.18±0.02),(0.17±0.02) and(0.19±0.04)h^-1,elimination half-life time(t_1/2) were(3.85±0.52),(4.12±0.59) and(3.85±0.77)h.For low dosage of oral administration after meal,the AUC_0→12 of famotidine was(257.94±39.88)μg·h·L^-1,t_max was(2.83±0.39)h,ρ_max was(64.56±2.18)μg·L^-1,k was(0.20±0.04)h^-1,t_1/2 was(3.54±0.69)h.For multiple dosage administration after steady state,the AUC_0→τof famotidine was(310.02±23.95)μg·h·L^-1,t_max was(2.46±0.33)h,steady state trough plasma concentration(ρ^SS_min) was(7.84±1.31)μg·L^-1 and peak plasma concentration(ρ^SS_max) was(60.78±2.13)μg·L^-1 respectively,average plasma concentration(ρ^SS) after steady state was(25.83±2.00)μg·L^-1,k was(0.20±0.03)h^-1,t_1/2 was(3.61±0.54)h,degree of fluctuation(DF) was 2.06,accumulation index was 0.02.CONCLUSION q-test was performed on the ratio of AUC_0→12 to dose of low,middle and high dosage oral administration without meal.The pharmacokinetics of compound famotidine chewing tablets in vivo accorded with linear process.Variance test was performed on pharmacokinetic parameters of administration without and with meal.Food had no effect on pharmacokinetics of famotidine in vivo.The multiple administration showed no accumulation in vivo.