甲巯咪唑大鼠经皮给药的药代动力学  

Pharmacokinetics of Thiamazole Following Transdermal Administration in Rats

作　　者：柳晓泉[1] 耿芳[1] 王松磊[1] 周曙[1] 王广基[1] 

机构地区：[1]中国药科大学药物代谢研究中心,南京210009

出　　处：《中国药科大学学报》2005年第4期342-345,共4页Journal of China Pharmaceutical University

基　　金：国家高技术研究发展计划("八六三"计划)资助项目(No.2003AA2Z347A);江苏省药代动力学重点实验室资助项目(No.BM2001201)~~

摘　　要：目的:研究甲巯咪唑在大鼠体内经皮吸收的药代动力学,并与口服吸收动力学进行比较。方法:采用HPLC法测定大鼠口服(2 mg/kg)或经皮(1,2,4 mg/kg)给药后血清和甲状腺组织中的甲巯咪唑浓度。色谱柱为Lichrospher C18柱,流动相为甲醇-水(10∶90),流速1.0 min,柱温30℃,检测波长UV 254 nm。结果:口服或经皮(2 mg/kg)给药后,甲巯咪唑的tmax分别为1.5 h和2.5 h,cmax分别为1 716.6和817.2 ng/mL,AUC分别为4 606.2和3 739.6 ng.h/mL,t1/2分别为2.64 h和2.70 h,甲状腺组织中的药物浓度分别于给药后2 h和1 h达到峰值,其峰浓度分别为307.7和320.9 ng/50 mg。经皮给予高、中和低3个剂量甲巯咪唑后,其AUC与剂量呈现线性相关性。结论:甲巯咪唑口服给药的血药浓度明显高于经皮给药的血药浓度,但甲状腺组织中的药物浓度无显著性差异,提示经皮给药的全身不良反应小于口服给药。AIM:To study the pharmacokinetics of thiamazole after transdermal administration and compare it with oral pharmacokinetics in rats.METHODS:Thiamazole concentrations in serum and thyroid tissue after oral or transdermal administration of thiamazole in rats were determined by HPLC.Chromatographic analyses were performed on a Lichrospher C_(18) column.Methanol-water(10∶90) was used as the mobile phase with the UV detector set at 254 nm.RESULTS:Following oral and transdermal administration of thiamazole(2 mg/kg),t_(max) was 1.5 and 2.5 h,respectively,c_(max) was 1 716.6 and 817.2 ng/mL,respectively.The esimated AUC were 4 606.2 and 3 739.6 ng·h·mL^(-1),t_(1/2)were 2.64 and 2.70 h;drug concentrations in thyroid tissue reached their peak level at 2 and 1 h respectively after administration,the peak levels being 307.7 and 320.9 ng/50 mg respectively.Following transdermal administration of three dose of thiamazole(1,2,4 mg/kg),linearity between AUC and dose existed.CONCLUSION:Thiamazole concentration in serum after oral administration was much higher than that after transdermal administration,but the concentrations in thyroid tissues were similar following oral and trandermal administration.It suggests that the systemic side effect of transdermal administration of thiamazole might not be as significant as that of oral administration.

关 键 词：甲巯咪唑 药物动力学 经皮 高效液相色谱法 

分 类 号：R96[医药卫生—药理学]