Pharmacokinetics of flutamide and its metabolite 2-hydroxyflutamidein normal and hepatic injury rats  

Pharmacokinetics of flutamide and its metabolite 2 hydroxyflutamide in normal and hepatic injury ratsc2

作　　者：许长江[1] 李端[1] 

机构地区：[1]上海医科大学药学院药理学教研室

出　　处：《中国药理学报》1998年第1期39-43,共5页Acta Pharmacologica Sinica

摘　　要：目的：建立一新的高压液相色谱法用来研究氟他胺（Ｆｌｕ）及其活性代谢产物２羟基氟他胺（ＨＦ）的药物动力学．方法：正常及肝损伤大鼠灌胃Ｆｌｕ５０ｍｇ·ｋｇ－１．采用反相高压液相色谱法，以甲基睾丸素为内标，流动相为甲醇∶乙腈∶水∶乙醚＝４０∶２０∶３５∶１（体积比），检测波长为２３４ｎｍ．结果：Ｆｌｕ的Ｋ与Ｃｌ分别由０６２±０１６ｈ－１及６０±１０Ｌ·ｋｇ－１·ｈ－１减小到０１６±００３ｈ－１及０６３±０２９Ｌ·ｋｇ－１·ｈ－１（Ｐ＜００１），ＡＵＣ与Ｃｍａｘ分别由８６±１３ｍｇ·Ｌ－１·ｈ及２４±０７ｍｇ·Ｌ－１增加到１００±４４ｍｇ·ｋｇ－１·ｈ及６７±２８ｍｇ·Ｌ－１（Ｐ＜００１）．ＨＦ的Ｋ（ｍ）由００７±００１ｈ－１减小到００５±００１ｈ－１（Ｐ＜００１）．结论：在肝损伤大鼠，Ｆｌｕ与ＨＦ消除受到显著抑制．AIM: To develop a new HPLC assay to study the pharmacokinetics of flutamide (Flu) and its active metabolite 2 hydroxyflutamide (HF) in rats. METHODS: Normal or hepatic injury rats were given ig Flu 50 mg·kg -1 . Reverse phase HPLC was developed with a μ Bondapak C 18 column. Internal standard was methyltestosterone. The mobile phase was a mixture of methanol∶acetonitrile∶water∶diethyl ether=40∶20∶35∶1 (vol). Absorbance was measured at λ 234 nm. RESULTS: The pharmacokinetic parameters of Flu were as follows: in normal rats, K =0 62±0 16 h -1 , Cl =6 0±1 0 L·kg -1 ·h -1 , AUC=8 6±1 3 mg·L -1 ·h, C max =2 4±0 7 mg·L -1 ; in hepatic injury rats, K =0 16±0 03 h -1 , Cl =0 63±0 29 L·kg -1 ·h -1 , AUC=100±44 mg·L -1 ·h, C max =6 7±2 8 mg·L -1 . The pharmacokinetic parameters of HF were as follows: in normal rats, K (m) =0 07±0 01 h -1 , AUC=219±22 mg·L -1 ·h, C max =8 6±0 6 mg·L -1 ; in hepatic injury rats, K (m) =0 05±0 01 h -1 , AUC=170±42 mg·L -1 ·h, C max =3 8±0 8 mg·L -1 . There were significant differences between the parameters of normal and hepatic injury rats ( P <0 01) except AUC of HF ( P >0 05). CONCLUSION: This HPLC assay was sensitive and precise, and the elimination of Flu and HF was inhibited significantly due to hepatic injury.

关 键 词：氟他胺 羟基氟他胺 药物动力学 四氯化碳 肝损伤 

分 类 号：R979.1[医药卫生—药品]