摘要
目的 研究合用环孢素（Ｃｙｓ）前后硫唑嘌呤（ＡＺＰ）血药浓度及药物动力学变化。方法 ９只家兔灌胃法给硫唑嘌呤（２０ｍｇ·ｋｇ－１）后，高效液相色谱法（ＨＰＬＣ）测定ＡＺＰ和其主要代谢物６巯基嘌呤（６ＭＰ）的血药浓度，１ｗｋ后，灌胃给Ｃｙｓ（１５ｍｇ·ｋｇ－１，ｑｄ）共４ｄ，并于ｄ４灌胃给Ｃｙｓ后ｌｈ再以同样方式给ＡＺＰ，同法测定ＡＺＰ和６ＭＰ血药浓度，以３Ｐ８７药物动力学程序拟合药物动力学参数。结果 正常家兔合用环孢素后，６ＭＰ的Ｖｃ升高，由合用前（１５９－１±２４－２）升至合用后（２６９－９±１１８－０）Ｌ·ｋｇ－１（Ｐ＜０－０５），ＣＬ升高，由（１－６±０－４）升至（３－２±２－０）Ｌ·ｍｉｎ－１·ｋｇ－１（Ｐ＜０－０５），ＡＵＣ降低，由（７７－９７±２６－０２）降至（４７－０１±２２－７０）ｍｉｎ·μｍｏｌ·Ｌ－１（Ｐ＜０－０５）。其他药动学参数变化差异无显著性。结论 合并用药可引起Ｖｃ、ＣＬ升高，ＡＵＣ降低。
AIM To study changes of azathioprine (AZP) serum concenstrationsand pharmacoki netics in rabbits, before and after oral administration cyclosporin A (CsA) METHODS Nine rabbits were first single administred AZP (dose:20 mg·kg, once times of daily), serum concenstration of AZP and its metabolite 6 mercaptoprine (6 MP) in different time were determined by high performance liquid chormatography (HPLC), after a week, CsA had been administred for four days (15 mg·kg -1 , once times of daily), and the fourth day, AZP were concurrently administred, AZP and 6 MP were determined by same methods RESULTS and CONCLUTIONS The metabolism of 6 MP was two compartment model, the apparent oral clearance(CI) and the volume of distribution of the central compartment (Vc) and aera under the C t curve (AUC) of 6 PM were significantly different from single oral AZP and AZP in combination with CsA, Cl and Vc were increased 200% and 170%, AUC was decreased 166%, P <0 05
出处
《中国药理学通报》
CAS
CSCD
北大核心
1999年第6期557-560,共4页
Chinese Pharmacological Bulletin
