Open AccessComparative Metabolism of Batracylin (NSC 320846) and Nacetylbatracylin (NSC 611001) Using Human, Dog, and Rat Preparations In Vitro
Author(s) -
Joseph M. Covey,
Joel M. Reid
Publication year - 2016
Publication title -
journal of drug metabolism and toxicology
Language(s) - English
Resource type - Journals
ISSN - 2157-7609
DOI - 10.4172/2157-7609.1000203
Subject(s) - microsome , metabolite , biochemistry , cytochrome p450 , metabolism , carcinogen , demethylation , hepatocyte , toxicity , biology , in vitro , chemistry , microbiology and biotechnology , dna methylation , gene expression , organic chemistry , gene
Batracylin is a heterocyclic arylamine topoisomerase inhibitor with preclinical anticancer activity. Marked species differences in sensitivity to the toxicity of batracylin were observed and attributed to differential formation of N-acetylbatracylin by N-acetyltransferase. A Phase I trial of batracylin in cancer patients with slow acetylator genotypes identified a dose-limiting toxicity of hemorrhagic cystitis. To further explore the metabolism of batracylin and N-acetylbatracylin across species, detailed studies using human, rat, and dog liver microsomal and hepatocyte preparations were conducted.