Acute treatment with pyrrolo(1,4)benzodiazepine antitumor antibiotics alters in vitro hepatic drug metabolizing activity in rats

John E. Atkinson, William C. Lubawy

Research output: Contribution to journalArticle

Abstract

The pyrrolo(1,4)benzodiazepine antitumor antibiotic, anthramycin, shares a number of toxicities with the widely used anticancer agent adriamycin. We investigated whether acute doses of anthramycin and the structurally related compounds, sibiromycin and tomaymycin, would depress P-450-dependent drug biotransformations as has been reported for adriamycin. Alterations in drug metabolism rates were determined in rats using 50 and 75% of the approximate 7-day LD50 determined in mice. 4 days post dosing ethylmorphine demethylase and aniline hydroxylase activities in liver 9000 g supernatant were depressed from 26 to 76%. Tomaymycin lowered drug metabolism in a dose-related manner, while sibiromycin produced the greatest amount of depression. Like adriamycin, the pyrrolo(l,4)benzo-diazepines possess the ability to depress hepatic drug metabolism and therefore may affect the disposition of compounds with which they are co-administered.

Original languageEnglish
Pages (from-to)337-342
Number of pages6
JournalToxicology Letters
Volume18
Issue number3
DOIs
StatePublished - 1 Jan 1983

Keywords

  • aniline hydroxylase
  • Anthramycin
  • ethylmorphine n-demethylase
  • hepatic drug metabolizing activity
  • sibiromycin
  • tomaymycin

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