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 language | English |
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Pages (from-to) | 337-342 |
Number of pages | 6 |
Journal | Toxicology Letters |
Volume | 18 |
Issue number | 3 |
DOIs | |
State | Published - Sep 1983 |
Keywords
- Anthramycin
- aniline hydroxylase
- ethylmorphine n-demethylase
- hepatic drug metabolizing activity
- sibiromycin
- tomaymycin