TY - JOUR T1 - Isolation and Identification of Major Urinary Metabolites of Rifabutin in Rats and Humans JF - Drug Metabolism and Disposition JO - Drug Metab Dispos SP - 963 LP - 969 VL - 25 IS - 8 AU - Ilya Utkin AU - Tatiana Koudriakova AU - Toni Thompson AU - Charles Cottrell AU - Eugenia Iatsimirskaia AU - John Barry AU - Paul Vouros AU - Nicholas Gerber Y1 - 1997/08/01 UR - http://dmd.aspetjournals.org/content/25/8/963.abstract N2 - The antimycobacterial drug rifabutin is extensively metabolized in humans and laboratory animals. About 40% of the dose is excreted in urine as unchanged drug, and lipophilic (extractable with 1-chlorobutane) and polar metabolites. Polar metabolites accounted for 59.1 ± 2.5% and 88.8 ± 4.4% of radioactivity in urine collected over 96 hr after intravenous administration of 25 and 1 mg/kg of [14C]rifabutin to Sprague-Dawley rats, respectively. After 48 hr, all urinary radioactivity consisted of polar metabolites. The most abundant polar metabolite, identified by electrospray ionization-MS, collision-induced dissociation-MS, and comparison of HPLC retention times with the synthetic standard, wasN-isobutyl-4-hydroxy-piperidine. Lipophilic metabolites accounted for <20% of urinary radioactivity. Major lipophilic metabolites, 25-O-deacetyl-rifabutin, 27-O-demethyl-rifabutin, 31-hydroxy-rifabutin, 32-hydroxy-rifabutin, and 20-hydroxy-rifabutin were isolated from both human and rat urine by HPLC and identified by electrospray ionization-MS, collision-induced dissociation-MS, and NMR spectrometry. In addition, two metabolites formed by the oxidation of theN-isobutyl-piperidyl group of rifabutin were found in the urine of rats, but not humans. The American Society for Pharmacology and Experimental Therapeutics ER -