Pharmacokinetics and Metabolism of Adriamycin and Daunomycin

Daunomycin (Daunorubicin) and Adriamycin and Structural Analogues: Biological Activity and Mechanism of Action

“…Besides the described transformation product, a small amount of another substance with a different Rf was observed in thin layer chromatography. More recent studies (BACHUR and GEE, 1971;BAcHUR, 1971;YESAIR et at., 1971) have cleared up the major pathway of daunorubicin metabolism in tissue homogenates.…”

“…In mice, 50% excretion of the drug occurs in about 24 hours in the case of daunomycin, and in about 32 hours in the case of adriamycin; moreover, drug accumulation in tissues is more pronounced after adriamycin than after daunomycin subacute treatment (DI FRONZO et at., 1971). The calculated" concentration x time" (C x t) in the case adriamycin equivalents has been demonstrated in all tissues to be several times greater than that found for daunomycin or its metabolite (YESAIR et at., 1971). Preliminary work (DI MARCO et aI., 1967 b;DI MARco and RUSCONI, 1967) provided evidence of extensive metabolism of daunomycin by liver homogenates.…”

“…The presence of the hydroxyl group at position 14 of the chromo ph ore protects against the metabolic transformation; as a matter of fact, no metabolic product, like daunorubicinol, was observed by incubation of adriamycin with tissue homogenates or in excreted materials (YESAIR et at., 1971;DI FRONZO et at., 1971). These findings are consistent with the higher toxicity and activity of adriamycin in vivo.…”

Effects of the anti-cancer drug adriamycin on the energy metabolism of rat heart as measured by in vivo 31P-NMR and implications for adriamycin-induced cardiotoxicity

“…Thereafter, phosphocreatine peak intensities remained stable at the lower level for at least 2.5 h which was the longest time tested in these acute experiments. It is interesting to note, that the time dependence of the adriamycin-induced decrease in heart phosphocreatine levels is similar to the time-dependence of drug clearance from plasma of rats after an intravenous bolus injection of comparable doses [24,25]. Half-times of plasma clearance and uptake into the various tissues, including heart, were reported to be 15 20 min.…”

Determination of Doxorubicin and Doxorubicinol in Plasma of Cancer Patients by High-Performance Liquid Chromatography

“…In the past decades, numerous analytical methods have been described for the determination of doxorubicin and its metabolites, including assays based on radiolabeled drug measurement (14), fluorometry (15), thin-layer chromatography (16), and HPLC (17-21). The available HPLC methods have generally employed ultraviolet, electrochemical, or fluorescence detection, and most have relied upon tedious and expensive solidphase extraction (SPE) techniques.…”