POSSIBLE RELEVANCE OF N-TRIFLUOROACETYLADRIAMYCIN (AD 41) IN THE ANTI-TUMORAL ACTIVITY OF N-TRIFLUOROACETYLADRIAMYCIN-14-VALERATE (AD 32) IN TUMOR-BEARING MICE .1. PHARMACOKINETIC EVIDENCE

  • 1 January 1980
    • journal article
    • research article
    • Vol. 64  (8-9) , 873-878
Abstract
AD 32 is an analog of doxorubicin whose chemico-physical characteristics are nontypical compared to the parent compound. Its most interesting feature is the lack of capacity to intercalate with DNA; thus, its mechanism of action as an antitumoral drug is still unknown. The N-trifluoroacetyl bond on the glycoside moiety is very stable and does not easily undergo enzymatic hydrolysis. Conversely, the valerate ester is split very rapidly by tissue and blood hydrolases. A kinetic study was presented on AD 32, and the formation and disappearance of its metabolite, AD 41 was followed. Peak levels, areas under the curve, and .beta.-half-lives of AD 32 and AD 41 after an i.v. injection of 80 mg/kg of AD 32 to Lewis lung carcinoma-bearing mice are presented. The results indicated very rapid disappearance of AD 32 from blood and tissues, whereas AD 41 persisted for much longer. All of the tissues taken into consideration were able to hydrolyze AD 32 to AD 41, suggesting that this compound plays an important role in the antitumoral activity of AD 32.