O-GLUCURONIDATION, A NEWLY IDENTIFIED METABOLIC PATHWAY FOR TOPOTECANAND N-DESMETHYL TOPOTECAN

During topotecan analysis of clinical urine samples, an additional pea k eluting just after the solvent front was observed, This potential me tabolite was isolated by chromatographic methods. Mass spectrometry da ta along with chromatographic retention data and fluorescence characte ristics showed that the isolated fractions contained two compounds, i. e. topotecan-O-glucuronide and N-desmethyl topotecan-O-glucuronide. Th e concentrations of the metabolites in human urine were relatively low , When topotecan was given as a 30 min infusion at a dosage of 1.5 mg/ m(2) daily for five consecutive days every 3 weeks, the maximal metabo lite concentrations in a 24 h urine sample were approximately 10% of t opotecan-O-glucuronide and 3.5% of N-desmethyl topotecan-O-glucuronide with respect to the concentration of topotecan in the urine. This is the first report demonstrating that glucuronide metabolites of topotec an are present in the urine of treated patients. [(C) 1998 Lippincott Williams & Wilkins.].