Possible relevance of N-trifluoroacetyladriamycin (AD 41) in the antitumoral activity of N-trifluoroacetyladriamycin-14 (AD 32) in tumor-bearing mice. I. Pharmacokinetic evidence

N-Trifluoroacetyladriamycin-14-valerate (AD 32) is an analog of doxorubicin whose chemico-physical characteristics are notypical compared to the parent compound. Its most interesting feature is the lack of capacity to intercalate with DNA; ths, its mechanism of action as an antitumoral drug is still unknown. The N-trifluoroacetyl bond on the glycoside moiety is vey stable and does not easily undergo enzymatic hydrolysis. Conversely, the valerate ester is split very rapidly by tissueand blood hydrolases. In this paper we present a kinetic study on AD 32, and we additionally follow the formation and disppearance of its metabolite, N-trifluoroacetyladriamycin (AD 41). Peak levels, areas under the curve, and β-half-lives of A 32 and AD 41 after an iv injection of 80 mg/kg of AD 32 to Lewis lung carcinoma-bearing mice are presented. The results ndicated very rapid disappearance of AD 32 from blood and tissues, whereas AD 41 persisted for much longer. Moreover, allof the tissues taken into consideration were able to hydrolyze AD 32 to AD 41, suggesting that this compound plays an imprtant role in the antitumoral activity of AD 32.