Hepatobiliary metabolism and excretion of adriamycin and N-trifluoroacetyladriamycin-14-valerate in the rat.
In connection with mechanism of action studies with N-trifluoroacetlyadriamycin-14-valerate (AD 32), a superior Adriamycin (ADR) analog under development in these laboratories, serial bile samples were collected from male Sprague-Dawley rats given a single i.v. dose of either ADR (4 mg/kg) or AD 32 (20 mg/kg) and were analyzed for anthracyclines by thin-layer chromatography-fluorometry and high-performance liquid chromatography. For ADR, 20% of the administered dose was accounted for at 24 hr, whereas 80% of the AD 32 dose were excreted into the bile by this time. ADR underwent little biotransformation; 80% of the 48-hr cumulative fluorescence excretion was attributable to unchanged drug, one-half the remainder was adriamycinol, and the balance was polar conjugates. In contrast, AD 32 underwent extensive metabolism to N-trifluoracetyladriamycin, N-trifluoroacetyladriamycinol, and polar conjugates, mostly glucuronides of N-trifluoroacetyladriamycin and N-trifluoroacetyladriamycinol. Based on direct and indirect evidence, ADR was not a metabolite of AD 32.
D000818:Animals; D001646:Bile / Q000032:analysis; D001711:Biotransformation; D002853:Chromatography, Liquid; D002855:Chromatography, Thin Layer; D004317:Doxorubicin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000378:metabolism*; D005453:Fluorescence; D005966:Glucuronidase; D007275:Injections, Intravenous; D008099:Liver / Q000378:metabolism*; D008297:Male; D051381:Rats; D013997:Time Factors; D014269:Trifluoroacetic Acid / Q000378:metabolism
D004317:Doxorubicin; D014269:Trifluoroacetic Acid; D005966:Glucuronidase