Utkin I, Koudriakova T, Thompson T, Cottrell C, Iatsimirskaia E, Barry J, Vouros P, Gerber N
Department of Pharmacology, College of Medicine, The Ohio State University, Columbus 43210, USA.
Drug Metab Dispos. 1997 Aug;25(8):963-9.
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, was N-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 the N-isobutyl-piperidyl group of rifabutin were found in the urine of rats, but not humans.
抗分枝杆菌药物利福布汀在人和实验动物体内会被广泛代谢。约40%的剂量以原形药物、亲脂性（可用1-氯丁烷提取）和极性代谢物的形式经尿液排泄。给Sprague-Dawley大鼠静脉注射25mg/kg和1mg/kg的[14C]利福布汀后，在96小时内收集的尿液中，极性代谢物分别占放射性的59.1±2.5%和88.8±4.4%。48小时后，所有尿液放射性均由极性代谢物组成。通过电喷雾电离质谱、碰撞诱导解离质谱以及与合成标准品比较高效液相色谱保留时间鉴定出的最丰富的极性代谢物是N-异丁基-4-羟基哌啶。亲脂性代谢物占尿液放射性的比例小于20%。主要的亲脂性代谢物，25-O-去乙酰基利福布汀、27-O-去甲基利福布汀、31-羟基利福布汀、32-羟基利福布汀和20-羟基利福布汀，通过高效液相色谱从人和大鼠尿液中分离出来，并通过电喷雾电离质谱、碰撞诱导解离质谱和核磁共振光谱进行鉴定。此外，在大鼠尿液中发现了利福布汀的N-异丁基哌啶基团氧化形成的两种代谢物，但在人尿液中未发现。
