IDENTIFICATION OF THE GLUCURONIDE AND GLUTATHIONE CONJUGATES OF THE ANTITUMOR DRUG N2-METHYL-9-HYDROXYELLIPTICINIUM ACETATE (CELIPTIUM) - COMPARATIVE DISPOSITION OF THIS DRUG WITH ITS OLIVACINIUM ISOMER IN RAT BILE

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  • 1 January 1984
    • journal article
    • research article
    • Vol. 12  (1) , 111-119
Abstract
Two metabolites of the antitumor drug N-2-methyl-9-hydroxyellipticinium acetate (Celiptium) were isolated from bile of 10 mg/kg i.v.-treated rats. These metabolites were characterized by UV-visible, mass and proton-NMR data and identified as 9-(O)-glucuronide conjugate and 10-(S)-glutathione adduct. Evidence for the same type of metabolites for the isomer N-2-methyl-9-hydroxyolivacinium acetate was supported by HPLC [high-performance liquid chromatography] data. Despite their minor structural differences (change into a methyl position), the biliary excretion profile of these 2 drugs is rather different quantitatively; total metabolites excreted within a 12-h period is 33 .+-. 4% of the administered dose for ellipticinium and 70 .+-. 6% for olivacinium. The major metabolite is the 9-(O)-glucuronide conjugate for those 2 drugs, i.e., 25 .+-. 3% of the dose of ellipticinium and 67 .+-. 5% for olivacinium derivative. In both cases, the presence of the 10-(S)-glutathione adduct as a minor metabolite [1.5 .+-. 0.5 of the dose (ellipticinium) and 1 .+-. 0.5 (olivacinium)] supports the hypothesis that a biooxidative alkylation process could occur in vivo.