TY - JOUR T1 - 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. JF - Drug Metabolism and Disposition JO - Drug Metab Dispos SP - 111 LP - 119 VL - 12 IS - 1 AU - M Maftouh AU - B Monsarrat AU - R C Rao AU - B Meunier AU - C Paoletti Y1 - 1984/01/01 UR - http://dmd.aspetjournals.org/content/12/1/111.abstract N2 - Two metabolites of the antitumor drug N-2-methyl-9-hydroxyellipticinium acetate (Celiptium) were isolated from bile of 10 mg/kg iv-treated rats. These metabolites were characterized by UV-visible, mass and proton-NMR data and identified as (i) 9-(O)-glucuronide conjugate and (ii) 10-(S)-glutathione adduct. Evidence for the same type of metabolites for the isomer N-2-methyl-9-hydroxyolivacinium acetate was supported by HPLC data. Despite their minor structural differences (change into a methyl position), the biliary excretion profile of these two drugs is rather different quantitatively: total metabolites excreted within a 12-hr 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 two drugs: 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. ER -