羟基喜树碱(HCPT)不同给药方式的药理学比较  

A Comparison of Clinical Pharmacokinetic and Pharmacodynamic of Different Administration Schedules of Intravenous 1O-Hydroxycamptothecin

作　　者：李苏[1] 姜文奇[1] 张力[1] 廖海[1] 管忠震[1] 

机构地区：[1]中山医科大学肿瘤防治中心内科,广州510060

出　　处：《中国临床药理学杂志》2001年第6期427-430,共4页The Chinese Journal of Clinical Pharmacology

摘　　要：目的：比较羟基喜树碱（ＨＣＰＴ）不同给药方式的药代动力学行为和毒性。方法：剂量１２ｍｇ／ｍ２·ｄ－１按体表面积折算ＨＣＰＴ溶于０９％ＮａＣｌ液中。方案１：３０ｍｉｎ恒速静脉滴注，连用５ｄ；方案２：４ｈ静脉恒速静脉滴注，连用１０ｄ；方案 ３：８ｈ恒速静脉滴注，连用１０ｄ；停用后观察 ２周。同时于第 １，５，１０ｄ的给药前、停药即刻、给药后０，０．２５，０．５，１，２，４，６，８，１２ｈ静脉抽取２ｍｌ血置肝素化试管中，用高效液相荧光法测定ＨＣＰＴ在人体的血药浓度，３ｐ９７计算药代动力学参数。结果：随静脉滴注时间的增加，病人的主要药物不良反应发生率和程度降低。３０ｍｉｎ静脉滴注，４／６例出现Ⅰ－Ⅲ度粒细胞下降，１／６例出现腹泻，２／６例出现恶心、呕吐。４ｈ恒速静脉滴注有２／６例出现Ⅰ－Ⅱ度粒细胞下降和１／６出现Ⅰ度恶心、呕吐。８ｈ伍速静脉滴注，患者未见粒细胞下降，腹泻，恶心、呕吐。ＨＣＰＴ在体内呈二室模型，滴注３０ｍｉｎ的消除半衰期（ｔ１２β）：１．０３±０．５８ｈ．表观分布容积（Ｖｄ）：５５４±５．２Ｌ，清除率（ＣＬ）：９．０５±６．２Ｌ·ｈ－１；滴注４ｈ的ｔ（１２β）：３．８２±０．９６ｈ，Ｖｄ１８．１±５．OBJECTIVE:Comparing pharmacokinetic and toxicity of 10- hydroxycamptothecin on different intravenous administrion. METHODS:Doseinitiated at 12mg.m2,was solved in 0.9%Ncl 1OOml, given as follows:(a)30min constant infusion for 5consecutive days;(b)4h constant infusion for 10 consecutive days; (c)8h constant infusion for 10 consecutive days. Patients were evaluated for response after two weeks. Heparinized blood samples(2m1) were collected on the day 1,5,10 day, immediately predose (time 0), then postinfusion at 0,15,30 minutes, and 1,2,4,6,8,12 hours. Pharmacokinetic analysis was performed in 18 patients using a validated high-performance liquid chromatographic assay and 3p97. RESULTS: Infusion time increasing from 30mm to 8h, the main adverse intensity and incidence rate decreased accordingly. (a)30min constant infusion, 4/6 patients experienced I- III grade neutorpenia, 1/6 had diarrhea and 3/6had nausea and vomiting. (b)4h infusion, 2/6 experienced I-IT grade neutropenia and nausea and vomiting.C:8h infusion, no patient experienced any toxicity. A two-compartment model was used to fit the plasma concentration-time curve;with a terminal elimination half-life(t1/2,β) of 1.03 ±0.58h 3 82 + 0.96h, 3.41 ±1.05h respectively. Distributon volumes (Vd) is 5.54 ±5.2L 18.1 ± 5.7L. 25.4 ±8.3L respectively. CONCLUSION:Infusion time rising from 30mm to 4h, t1/2,β and Vdincrease accordingly,but increasing to 8h, t1/2,β and Vd do not increasing accordingly with C decreasing. The incidence of toxicity occuring in 4h, 8h is less frequent than in 30mm.

关 键 词：羟基喜树碱 药代动力学 毒性 抗肿瘤药 给药方式 

分 类 号：R979.1[医药卫生—药品] R969.1[医药卫生—药学]