文章基本信息

标题：EFFECTS OF CHLORDIAZEPOXIDE, DIAZEPAM AND OXAZEPAM ON THE ANTITUMOR ACTIVITY, THE LETHALITY AND THE BLOOD LEVEL OF ACTIVE METABOLITES OF CYCLOPHOSPHAMIDE AND CYCLOPHOSPHAMIDE OXIDASE ACTIVITY IN MICE
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作者：KEN-ICHI SASAKI ; SHINOBU FURUSAWA ; GIICHI TAKAYANAGI 等
期刊名称：Biological and Pharmaceutical Bulletin
印刷版ISSN：0918-6158
电子版ISSN：1347-5215
出版年度：1983
卷号：6
期号：10
页码：767-772
DOI：10.1248/bpb1978.6.767
出版社：The Pharmaceutical Society of Japan
摘要：Effects of Chlordiazepoxide, diazepam and oxazepam on the antitumor activity and acute toxicity of cyclophosphamide and the level of its active metabolites in the plasma were investigated in mice. Cyclophosphamide was administered 24 h after the final injection of chlordiazepoxide, diazepam or oxazepam (100 mg/kg/d for 3 d, i.p.). Pretreatment with these drugs increased the acute toxicity of cyclophosphamide (300 or 450 mg/kg, i.p.), whereas drugs had no effect on the antitumor activity of cyclophosphamide (100 mg/kg, i.p.) against Ehrlich solid carcinoma. A high level of active metabolites of cyclophosphamide in the plasma after the administration of cyclophosphamide (300 or 450 mg/kg, i.p.) was observed in chlordiazepocide-, diazepam- or oxazepam-treated mice. On the other hand, chlordiazepoxide, diazepam or oxazepam enhanced significantly the activity of cyclophosphamide oxidase in hepatic microsomes. It is concluded that potentiation of the acute toxicity at a high dose of cyclophosphamide by chlordiazepoxide, diazepam and oxazepam is due to an induction of microsomal drug-metabolizing enzyme which are responsible for the in vivo activation of cyclophosphamide.
关键词：mice