Brammer K W, Coakley A J, Jezequel S G, Tarbit M H
Clinical Research Department, Pfizer Central Research, Sandwich, Kent, United Kingdom.
Drug Metab Dispos. 1991 Jul-Aug;19(4):764-7.
The disposition and metabolism of 14C-labeled fluconazole (100 microCi) was determined in three healthy male subjects after administration of a single oral capsule containing 50 mg of drug. Blood samples, total voided urine, and feces were collected at intervals after dosing for up to 12 days post-dose. Pharmacokinetic analysis of fluconazole concentrations showed a mean plasma half-life of 24.5 hr. Mean apparent plasma clearance and apparent volume of distribution were 0.23 ml/min/kg and 0.5 liter/kg, respectively. There was no evidence of any significant concentrations of metabolites circulating either in plasma or blood cells. Mean total radioactivity excreted in urine and feces represented 91.0 and 2.3%, respectively, of the administered dose. Mean excretion of unchanged drug in urine represented 80% of the administered dose; thus, only 11% was excreted in urine as metabolites. Only two metabolites were present in detectable quantities, a glucuronide conjugate of unchanged fluconazole and a fluconazole N-oxide, which accounted for 6.5 and 2.0% of urinary radioactivity, respectively. No metabolic cleavage products of fluconazole were detected.
在三名健康男性受试者口服一粒含50 mg药物的胶囊后，测定了14C标记氟康唑（100微居里）的处置和代谢情况。给药后，每隔一段时间采集血样、全部尿液和粪便，直至给药后12天。氟康唑浓度的药代动力学分析显示，血浆平均半衰期为24.5小时。平均表观血浆清除率和表观分布容积分别为0.23 ml/（min·kg）和0.5升/千克。没有证据表明血浆或血细胞中有任何显著浓度的代谢物在循环。尿液和粪便中排泄的平均总放射性分别占给药剂量的91.0%和2.3%。尿液中未变化药物的平均排泄量占给药剂量的80%；因此，只有11%以代谢物形式经尿液排泄。仅检测到两种可定量的代谢物，即未变化氟康唑的葡糖醛酸共轭物和氟康唑N-氧化物，它们分别占尿液放射性的6.5%和2.0%。未检测到氟康唑的代谢裂解产物。
