硝苯地平在正常及肝纤维化大鼠体内的药动学研究

Pharmacokinetics of nifedipie in normal and hepatic fibrosis rats

目的：研究肝纤维化对硝苯地平在大鼠体内药动学的影响。方法：正常大鼠及肝纤维化大鼠分别灌胃（ig）给予硝苯地平,应用HPLC测定不同时间点血药浓度,利用DAS 2.1.1.软件计算药动学参数,SPSS 17.0软件进行统计分析。结果：在10 mg·kg-1组和5 mg·kg-1剂量组中,模型鼠AUC0~t和AUC0~∞较正常鼠的显著增大,说明肝纤维化大鼠对于药物的吸收程度明显增加;MRT0~t,MRT0~∞和t1/2显著增大,CL/F显著减小,表明硝苯地平在体内的代谢速率减慢,影响了药物的消除过程;5 mg·kg-1组中还出现了Cmax增加、V/F显著减小,说明肝纤维化对硝苯地平的吸收及分布产生影响。结论：肝纤维化对硝苯地平在大鼠体内的吸收、分布、消除等药动学行为会产生显著影响。

Objective： To observe the effect of hepatic fibrosis on the pharmacokinetics of nifedipine in rats. Methods： Tweety-four Spraque-Dawley rats were divided into four groups（ normal and hepatic fibrosis group）and administered nifedipine by gavage at the dose of 10 and 5 mg·kg- 1. The plasma concentration was analyzed by HPLC at different time. The pharmacokitnetic parameters were caculated with DAS 2. 1. 1 and statistically analyzed by SPSS 17. 0. Results： Compared with normal group,the pharmacokinetic parameters AUC0 ~ tand AUC0 ~ ∞in hepatic fibrosis group increased significantly,indicating more drug was absorbed in rats with hepatic fibrosis. There were significant differences between normal group and model group in pharmacokinetic parameters of MRT0 ~ t,MRT0 ~ ∞,t1 /2,CL/F,and V/F（ P〈0. 05）,which implied that the distribution and elimination were affected by hepatic fibrosis. Conclusion： Hepatic fibrosis can affect the absorption,distribution,and elimination of nifedipine in rats evidently.