PRECLINICAL PHARMACOKINETICS AND ANTITUMOR-ACTIVITY OF IMEXON

被引:17
作者
DORR, RT
LIDDIL, JD
KLEIN, MK
HERSH, EM
机构
[1] ARIZONA CANC CTR,COLL MED,DEPT INTERNAL MED,HEMATOL ONCOL SECT,TUCSON,AZ 85724
[2] SW VET ONCOL,TUCSON,AZ 85719
关键词
IMEXON; PHARMACOKINETICS; AZIRIDINES; LEUKEMIA;
D O I
10.1007/BF00872858
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Imexon is an aziridine compound originally studied for immune-enhancing effects on lymphocytes. The drug was well-tolerated in humans and was shown to be active in a variety of animal tumor models. Recently, imexon has demonstrated antitumor activity in human multiple myeloma cell lines in vitro. The pharmacokinetics of the compound using a normal phase HPLC assay were studied in normal mice and in dogs with mast cell tumors. Doses of 100 mg/kg given intraperitoneally produced peak plasma levels over 100 mu g/ml in mice and the drug was rapidly eliminated with half lives of 8 minutes (alpha phase) and 29 minutes (beta phase). Only 20% of an oral imexon dose was absorbed in the mouse. In dogs, the alpha and beta phase half lives ranged from 18-26 minutes and 91-110 minutes, respectively. Peak levels over 100 mu g/ml were obtained following intravenous doses of 12.5 mg/kg and 25 mg/kg. Imexon was active in mice bearing either P-388 or L-1210 leukemia, but not in mice with B-16 melanoma. These results suggest that cytotoxic drug concentrations can be obtained in vivo and that imexon is active in lymphoproliferative tumors.
引用
收藏
页码:113 / 116
页数:4
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