Pharmacokinetics of CPT-11 in rhesus monkeys

被引：0

作者：

Inaba M. ^{[1
]}

Ohnishi Y. ^{[2
]}

Ishii H. ^{[2
]}

Tanioka Y. ^{[2
]}

Yoshida Y. ^{[3
]}

Sudoh K. ^{[3
]}

Hakusui H. ^{[3
]}

Mizuno N. ^{[4
]}

Ito K. ^{[4
]}

Sugiyama Y. ^{[4
]}

机构：

[1] Cancer Chemotherapy Center, Japan. Found. for Cancer Research, Toshima-ku, Tokyo 170

[2] Ctrl. Inst. for Experimental Animals, Miyamae-ku, Kawasaki, Kanagawa 216

[3] Drug Metab./Analyt. Chem. Res. Lab., Daiichi Pharmaceutical Co., Ltd., Edogawa-ku, Tokyo 134

[4] Faculty of Pharmaceutical Sciences, University of Tokyo, Bunkyo-ku, Tokyo 113

来源：

Cancer Chemotherapy and Pharmacology | 1997年 / 41卷 / 2期

关键词：

CPT-11; Monkey; Pharmacokinetics;

D O I：

10.1007/s002800050715

中图分类号：

学科分类号：

摘要：

Purpose: To examine the pharmacokinetic relationships between humans and monkeys, we studied the disposition of 7-ethyl-10-[4-(1-piperidino)-1- piperidino]carbonyloxycamptothecin (CPT-11) and its active metabolite, 7- ethyl-10-hydroxycamptothecin (SN-38), in rhesus monkeys. Methods: CPT-11 was administered to a total of six monkeys at doses of 3, 7, 15 and 25 mg/kg by intravenous infusion for 10 min and plasma concentrations and pharmacokinetic parameters of CPT-11 determined. Results: Maximum plasma concentrations at 25 mg/kg reached around 10 000 ng/ml, and dropped to 500 ng/ml in 8 h. Plasma concentrations of SN-38 remained between 2 and 10 ng/ml. Mean values of systemic clearance, mean residence time and distribution volume at steady state, the major pharmacokinetic parameters for CPT-11, were 13.3 (ml/min per kg), 192 (min) and 2553 (ml/kg), respectively. The initial plasma concentration ratio of lactone to total CPT-11, 76%, declined to about 20% within 75 min, and the final ratio was about 40% at 8 h; the initial ratio of SN-38 was 72%, dropped to 34% within 70 min and finally recovered to 55% at 8 h. Conclusion: Comparison with human data revealed that systemic clearances of CPT-11 and the maximum AUC of SN-38 were not as different between humans and monkeys as between humans and mice, but the metabolic conversion of CPT- 11 into SN-38 in monkeys was significantly lower than in humans.

引用

页码：103 / 108

页数：5

共 21 条

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