上消化道出血儿童法莫替丁的药动学和药效学研究

Pharmacokinetics and Pharmacodynamics of Famotidine in Chinese Children with Upper Gastrointestinal Bleeding

目的:研究上消化道出血儿童法莫替丁的药动学和药效学。方法:采用高效液相色谱法测定血清中法莫替丁浓度,以DAS 药代动力学程序计算药代动力学参数,24 h 动态胃内 pH 监测来评价药效。结果:上消化道出血儿童首次静脉滴注法莫替丁(0.9 mg·kg^(-1)),t_(1/2)为(1.70±0.80)h,Vd 为(2.01±1.06)L·k^(-1),XL 为(0.54±0.28)L·h^(-1)·kg^(-1);胃内 pH>4的持续时间约为6 h。结论:静脉滴注法莫替丁(0.9 mg·kg^(-1))可显著抑制胃酸分泌,抑酸作用滞后于血药浓度。儿童不同个体间的药动学差异较大。

Objective：To evaluate the pharmacokinetics and pharmacodynamics of famotidine in children with upper gastrointestinal bleeding. Methods： 15 children with upper gastrointestinal bleeding（ranging from 4. 0 to 15.0 years of age and 14. 0 to 45.0 kg in weight）received 0. 9 mg· kg^-linfusion dose of famotidine. Plasma concentrations were determined with HPLC, and pharmacokinetics parameters were calculated with DAS pharmacokinetic program. 24 - h intragastric pH monitoring was performed. Results： One - compartment model - dependent approach was used to characterize the disposition of famotidine. From the data ,the elimination halflife （t1/2）was （1.70 ± 0. 80 ） hours, the apparent volume of distribution （ Vd ） was （ 2. 01 ± 1. 06 ） L · kg^-1 and the plasma clearance （CL） was （0. 54 ± 0. 28 ） L · h^ - 1 · kg^ - 1 The duration of intragastric pH 〉 4 were about 6 hours. Conclusion： The infusion dose of famotidine （0. 9 mg· kg^- 1 ） can inhibit the gastric acid secretion remarkably, but there is a hysteresis between the inhibition effect of famotidine and the plasma concentrations, and there have individual differences in pharmacokinetics parameters of these children.