大剂量地塞米松对大鼠无肝期芬太尼药代动力学的影响

Changes of fentanyl pharmacokinetics in rats during anhepatic phase by treatment of large dose of dexamethasone

目的:研究大剂量地塞米松处理后大鼠无肝期药代动力学的影响,探讨芬太尼的肝外代谢及地塞米松对其盰外代谢的影响。方法:将30只大鼠随机分为对照组(A组),无肝期组(B组)和地塞米松处理无肝期组(C组),每组10只,其中,B组直接分离并夹闭大鼠盰门;C组于夹闭盰门前1 h,注入地塞米松20 mg/kg。单次20μg/kg芬太尼静脉注射后,不同时间分别采取血样,用高效液相色谱紫外法(HPLC)检测芬太尼血药浓度,DAS1.0软件计算药代动力学。结果:芬太尼动力学符合开放性三室模型,无肝期组消除半衰期(T1/2β)和曲线下面积(AUC)比对照组明显增大(P<0.01),清除率(CL)比对照组明显减小(P<0.01),地塞米松处理组T1/2β、AUC、CL较对照组无明显差异(P>0.05)。结论:肝脏是芬太尼代谢的主要器官,芬太尼存在肝外代谢,地塞米松可以增强芬太尼的肝外代谢。

Objective： To observe the changes of fentanyl pharmacokineties in rats during anhepatic phase by treatment of large dose of dexamethasone and to investigate the extrahepatic metabolism of fentanyl. Mehtods： 30 rats were randomly divided into 3 groups., normal group（group A）, anhepatic phase group（group B） and anhepatic phase group treated with dexamethasone（group C）. There were 10 rats in each group. In group B, the hepatic portal of these animals was dissociated and closed. In group C, dexamethasone 20 mg/kg was in（used before the occlusion of hepatic portal 1 h and the other treatment was the same as group B. After the single dose of fentanyl （20μg/kg） was injected intravenously, the blood samples of 3 groups at different time were collected and the serum concentration of fentanyl was determined. Then the parmacokineties parameters of fentanyl were calculated. Results： Pharmacokinetics of fentanyl corresponded with a three - compartment open model. As compared with group A, T1/2β prolonged remarkably, AUC increased and CL decreased significantly in group B（P〈0. 01）, but were similar to those in group C（P〉0. 05）. Conclusion： Liver is the main organ for fentanyl metabolism. There is the extrahepatic metabolism in fentanyl and dexamethasone can enhance this extrahepatic metabolism of fentanyl.