酮康唑及其栓剂在山羊体内的药代动力学研究

The study of pharmacokinetics of intravenous injection and vaginal suppository of ketoconazole in goats

目的：考察酮康唑的氯化钠溶液给山羊静脉推注后的药代动力学行为，研究酮康唑泡腾阴道栓在山羊体内的绝对生物利用度。方法：用本文建立的ＨＰＬＣ新的测试条件对８只山羊静脉给予酮康唑后的血浓度进行测定，以ＭＣＰＫＰ－８６程序软件处理数据。结果和结论：静脉推注４ｍｇ／ｋｇ酮康唑的ｃ－ｔ数据符合开放二室模型，主要药代动力学参数（ｘ±ｓ）：α为（５．５８±０．８７）ｈ－１，β为（０．５６±０．１５）ｈ－１，ＶＢ为（０．１７±０．０４）Ｌ／ｋｇ，Ｃｌｓ为０．１０±０．０２Ｌ／（ｋｇ·ｈ），ＡＵＣ０～７为（４６．１６±１３．７９）μｇ·ｈ／ｍｌ，平均滞留时间（ＭＲＴ，对数梯形法）为（１．２５±０．１５）ｈ。阴道给予栓剂４ｍｇ／ｋｇ的ｃ－ｔ数据符合一室一级吸收模型，主要药代动力学参数（ｘ±ｓ）：ｔ１／２为（２．６３±０．７７）ｈ，ｔｍａｘ为（１．４１±０．５４）ｈ，ｃｍａｘ（０．９８±０．４４）μｇ／ｍｌ，ＡＵＣ０～７为（３．３１±２．３４）μｇ·ｈ／ｍｌ，ＭＲＴ（对数梯形法）为（３．７０±０．６１）ｈ，绝对生物利用度Ｆａｂｓ为（７．０±４．４）％。

Objective: To study the pharmacokinetics of ketoconazole after intravenous injection and the absolute bioavailability of ketoconazole vaginal suppository in goats. Methods: HPLC was developed to detect the serum concentration of ketoconazole in new conditions. The data were dealed with MCPKP86. Results and Conclusion: The pharmacokinetics of ketoconazole after intravenous injection agreed with two compartment model. Main parameters(±s) were that α was (5.58±0.87) h-1; β was (0.56±0.15) h-1; Vβ was (0.17±0.04) L/kg,Cls was (0.10±0.02) L/(kg·h),AUC0～7 was (46.16±13.79)μg·h/ml,MRT was (1.25±0.15)h. The pharmacokinetics of vaginal suppository of ketoconazole agreed with single compartment model. Main parameters (±s) were that t1/2 was (2.63±0.77)h,tmax was (1.41±0.54)h; cmax was (0.98±0.44)μg/ml,AUC0～7 was (3.31±2.34)μg·h/ml,MRT was (3.70±0.61)h,Fabs was (7.0±4.4)%.