Journal of Drug Metabolism & Toxicology
Open Access
ISSN: 2157-7609
+44-20-4587-4809
ISSN: 2157-7609
+44-20-4587-4809
Joel M Reid
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