羟基喜树碱胶囊剂在小鼠体内的药代动力学及组织分布

Pharmacokinetics and Tissue Distribution of HCPT Capsules in Mice

目的 :研究羟基喜树碱 (HCPT)胶囊剂在小鼠体内的药代动力学及组织分布。方法 :用荧光分光光度法测定小鼠血浆及组织中HCPT含量 ,计算药代动力学参数。结果 :HCPT在0 01～0.5μg/ml浓度范围呈良好的线性关系 ;HCPT胶囊剂的血药浓度 -时间曲线符合二房室药代动力学模型 ;主要药代动力学参数T1/2α 为0 29h、T1/2β 为1 64h、AUC0～24 为14 73μg/ml、CL为12 53ml/h。HCPT在胃肠组织中AUCpo>AUCiv,P<0.05 ,而全身血中AUCpo<AUCiv ,P<0.05。结论 :口服给药途径可以提高HCPT在胃肠组织的局部浓度。利用这种给药途径可达到提高化疗指数。

OBJECTIVE:To study the pharmacokinetics and tissue distribution of hydroxycamptothecine(HCPT) capsules in mice METHODS:The contents of HCPT in mouse plasma and tissues were determined by fluorescence spectrophotometry The pharmacokinetic parameters were measured RESULTS:The calibration curves of HCPT revealed linearity in the range 0 01～0 5μg/ml The plasma concentration-time curves of HCPT capsules conformed to two-conpartment model of pharmacokinetics The major pharmacokinetic parameters were:T1/2α 0 29h,T1/2β 1 64h,AUC0～24 14 73μg/ml and CL 12 53ml/h HCPT in gastrointestinal tissue AUCpo>AUCiv,P<0 05,but in whole body blood AUCpo<AUCiv,P<0 05 CONCLUSION:The oral administration of drug can increase the local-concentration in gastrointestinal tissue,which can raise the index of chemotherapy and reduce the systemic side-effects