Journal of Drug Metabolism & Toxicology
Open Access

Joseph M Covey

Publications

• 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 Ames Joseph 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

  Abstract PDF

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