adriamycin-aglycone and esorubicin

In five cancer patients we have determined the pharmacokinetics of 4'-deoxydoxorubicin (4'-DOX), its alcoholic metabolite 4'-deoxydoxorubicinol and the occurrence of circulating 7-deoxyaglycone metabolites. The 7-deoxyaglycone of the alcohol metabolite, the major aglycone of Adriamycin (ADR) present in man, was not detected in any serum sample. The 7-deoxyaglycone of the parent drug, which appears in concentrations in excess of 30 ng/ml after ADR administration, was detected in only 2/5 patients in trace amounts. These preliminary data indicate a difference in biotransformation between ADR and 4'-DOX despite their close structural similarities.

Topics: Biotransformation; Chromatography, High Pressure Liquid; Doxorubicin; Female; Half-Life; Humans; Kidney Neoplasms; Male; Naphthacenes

4'-Deoxydoxorubicin (4'-DOX) is a new and structurally similar analogue of the anti-cancer drug adriamycin (ADR). Based on known pathways of metabolism of ADR a high-performance liquid chromatographic method for the separation and identification of 4'-DOX and five possible metabolites was developed. Sensitivity for serum is 10 ng/ml for 4'-DOX and its alcoholic product 4'-deoxydoxorubicinol (4'-DOL) and 2 ng/ml for four of its aglycone products with coefficients of variation in k' of less than 5% throughout the day. An extraction step with better than 80% recovery of 4'-DOX and five reference metabolites from serum is described. Analysis of patient sera identified two metabolite peaks. These co-eluted with the reference metabolites of 4'-DOL and the 7-deoxyaglycone of 4'-DOX. Pharmacokinetics of the parent drug followed a two-compartment model. Both the metabolites were produced quickly and disappeared quickly.

Topics: Biotransformation; Chromatography, High Pressure Liquid; Doxorubicin; Humans; Kinetics; Naphthacenes; Neoplasms