Journal of Drug Metabolism & Toxicology
Open Access
ISSN: 2157-7609
+44-20-4587-4809
ISSN: 2157-7609
+44-20-4587-4809
Joseph M Covey
National Cancer Institute, National Institutes of Health,
9609 Medical Center Drive, Bethesda, Maryland 20892
Tanzania
Research Article
Comparative 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, Sarah A Buhrow, Mary Kuffel, Chad Walden, Holger Behrsing and Matthew M AmesJoseph M Covey, Joel M Reid, Sarah A Buhrow, Mary Kuffel, Chad Walden, Holger Behrsing and Matthew M Ames
Background: 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. Methods: Batracylin or N-acetylbatracylin was incubated with microsomes and hepatocytes from human, rat, and dog liver and with CYP-expressing human and rat microsomes. Substrates and metabolites were analyzed by HPLC with diode array, fluorescence, radiochemical, or mass spectrome.. View More»
DOI:
10.4172/2157-7609.1000203