复方法莫替丁咀嚼片人体药动学研究

Pharmacokinetics of famotidine in health volunteers after single and multiple administration of its compound chew tablets

目的:进行健康志愿者复方法莫替丁咀嚼片单剂和多剂给药的药动学试验,为复方法莫替丁咀嚼片临床应用提供试验依据.方法:采用单剂和多剂口服给药设计,采用高效液相色谱法测定法莫替丁经时血浓度,计算法莫替丁的药动学参数.结果:单剂和多剂口服复方法莫替丁咀嚼片后t1/2分别为(3.7±0.8)h和(4.5±0.9)h,Tmx分别为(2.15±0.24)h和(2.10±0.21)h,Cmax分男别为(65.9±9.1)μg·L-1和(72.0±10.1)μg·L-1,AUC0～15分男别为(365.9±64.9)μg·L-1·h和(362.6±44.8)μg·L-1·h,AUC0～∞分别为(401.1±65.5)μg·L-1·h和(416.8±42.0)μg·L-1·h,Ke分别为(0.19±0.04)h-1和(0.20±0.01)h-1,MRT为(7.1±0.7)h和(7.9±0.7)h.多剂口服Cmin为(6.3±0.6)μg·L-1.结论:复方法莫替丁咀嚼片中法莫替丁主要药动学参数单剂给药与多剂给药无显著改变,多剂给药体内无蓄积,制剂中其他成分不影响法莫替丁的体内过程.

OBJECTIVE To study the pharmacokinetics of famotidine in health volunteers after single and multiple administration of its compound chew tablets. METHODS Samples were collected, the blood concentrations of famotidine were determined by HPLC and its pharmacokinetic parameters were calculated. RESULTS The famotidine pharmacokinetic parameters after single and muhiple doses were as follows： t1/2（h）（3. 7±0. 8） and （4. 5±0. 9）, Tmax（h） （2. 15±0. 24） and （2. 10±0. 21）, Cmax（μg·L^-1） （65.9±9. 1） and （72. 0 ± 10. 1）, AUC0～15（μg· L^-1·h） （365.9±64. 9）and （362. 6 ± 44. 8）, AUC0～∞g. L^-1·h） （401.1±65.5） and （416. 8 ± 42. 0）,Ke（h^-1） （0. 19±0. 04）and （0. 20 ±0.01）, MRT（h） （7. 1 ±0.7） and （47.9±0.7） respectively,and Cmin（μg.L^-1） （6.3±0. 6） for muhiple administration. CONCLUSION There is no significant difference in pharmacokinetic parameters of famotidine between single and multiple administration, no accumulation after muhiple administration. Other components such as Ca^2＋ and Mg^2＋ make no effects on famotidine absorption.