Vinge E, Midskov C, Arnold E
Acta Pharmacol Toxicol (Copenh). 1986 May;58(5):355-62. doi: 10.1111/j.1600-0773.1986.tb00121.x.
The disposition of 14C-labelled fenflumizole was studied in five healthy subjects who received 0.1 mg/kg of fenflumizole as single intravenous doses. Radioactivity was measured in whole blood, plasma, urine and feces from prior to until 168 hours after dose administration. Chemical determinations of fenflumizole and its two demethylated derivatives in plasma were made by HPLC followed by fluorescence detection. Concentrations of fenflumizole calculated from radioactivity in plasma were consistently higher than from chemical determinations, suggesting the presence of metabolites. Radioactivity in blood cells decreased more slowly than in plasma. Plasma concentrations versus time could be described by a four-compartment model, with a terminal half-life of 119 hours (median). About 50% of the dose was excreted with the faeces, and about 4% was recovered in the urine. Unchanged fenflumizole in the urine accounted for 0.0001% of the total dose. Renal clearance of radioactive material decreased at low concentrations of radioactive compound in plasma, which may indicate changes in unbound fraction of drug and metabolites, or a saturable tubular reabsorption process. The slow elimination of fenflumizole is consistent with slow release from tissues and/or enterohepatic recycling.
在5名健康受试者中研究了14C标记的芬氟米唑的处置情况，这些受试者接受了0.1mg/kg的芬氟米唑单次静脉注射剂量。在给药前直至给药后168小时，对全血、血浆、尿液和粪便中的放射性进行了测量。血浆中芬氟米唑及其两种去甲基化衍生物的化学测定通过高效液相色谱法（HPLC）并随后进行荧光检测来进行。由血浆中的放射性计算得出的芬氟米唑浓度始终高于化学测定结果，这表明存在代谢物。血细胞中的放射性下降速度比血浆中的慢。血浆浓度与时间的关系可用四室模型描述，终末半衰期为119小时（中位数）。约50%的剂量随粪便排出，约4%在尿液中回收。尿液中未变化的芬氟米唑占总剂量的0.0001%。血浆中放射性化合物浓度较低时，放射性物质的肾清除率下降，这可能表明药物和代谢物的游离分数发生了变化，或者存在可饱和的肾小管重吸收过程。芬氟米唑的缓慢消除与从组织中缓慢释放和/或肠肝循环一致。
