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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 study the effect of hepatic fibrosis on the pharmacokinetics of nifedipine in rats. Methods: Normal rats and hepatic fibrosis rats were given intragastric (ig) nifedipine, HPLC determination of plasma concentrations at different time points, the use of DAS 2.1.1 software to calculate pharmacokinetic parameters, SPSS 17.0 software statistics analysis. Results: In the 10 mg · kg-1 and 5 mg · kg-1 groups, the AUC0 ~ t and AUC0 ~ ∞ of the model mice were significantly higher than those of the normal mice, indicating that the degree of absorption of the drug by the liver fibrosis rats was significant Increase MRT0 ~ t, MRT0 ~ ∞ and t1 / 2 significantly increased, CL / F significantly reduced, indicating that nifedipine in vivo metabolic rate slowed down, affecting the drug elimination process; 5 mg · kg-1 group Cmax increased and V / F decreased significantly, indicating that hepatic fibrosis has an impact on the absorption and distribution of nifedipine. Conclusion: Liver fibrosis has a significant effect on the absorption, distribution, elimination and other pharmacokinetic behaviors of nifedipine in rats.