Vinge E, Arnold E, Rasmussen S N, Midskov C
Acta Pharmacol Toxicol (Copenh). 1985 Aug;57(2):121-9. doi: 10.1111/j.1600-0773.1985.tb00019.x.
Fenflumizole is a substituted triaryl-imidazole with anti-inflammatory activity. Its disposition in man was studied after single intravenous and oral doses to 8 healthy male volunteers. Formation of the prostanoids thromboxane B2 (TXB2) and 6-keto-prostaglandin F1 alpha (6-k-PGF1 alpha) in clotting blood was studied concomitantly. The pharmacokinetics after intravenous doses (0.1 mg/kg) could be fitted to a three compartment model and the half-lives (t 1/2) corresponding to the three phases were 2 min., 1 hour and 15 hours, respectively. The volume of distribution was 386 l and the plasma clearance 0.5 l per min. Oral doses (0.5 mg/kg) were rapidly absorbed (t 1/2 = 0.2 hr) and the following elimination from plasma had two phases with half-lives of 1 hour and 14 hours. Bioavailability was 50% due to a pronounced first-pass effect. The two metabolites mono- and didemethylfenflumizole were detected after both oral and intravenous doses and their maximum plasma concentrations occurred after 1-2 hours irrespective of the administration route. A concentration dependent depression of prostanoid formation was seen, the IC50 for TXB2 and 6-k-PGF1 alpha being 19 and 53 ng/ml respectively.
芬氟咪唑是一种具有抗炎活性的取代三芳基咪唑。在给8名健康男性志愿者单次静脉注射和口服给药后，研究了其在人体中的处置情况。同时研究了凝血血液中前列腺素血栓素B2（TXB2）和6-酮-前列腺素F1α（6-k-PGF1α）的形成。静脉给药剂量（0.1mg/kg）后的药代动力学可以用三室模型拟合，三个阶段对应的半衰期（t1/2）分别为2分钟、1小时和15小时。分布容积为386升，血浆清除率为每分钟0.5升。口服剂量（0.5mg/kg）吸收迅速（t1/2 = 0.2小时），随后血浆消除有两个阶段，半衰期分别为1小时和14小时。由于明显的首过效应，生物利用度为50%。口服和静脉给药后均检测到两种代谢产物单去甲基和双去甲基芬氟咪唑，无论给药途径如何，它们的最大血浆浓度在1-2小时后出现。观察到前列腺素形成呈浓度依赖性抑制，TXB2和6-k-PGF1α的IC50分别为19和53ng/ml。
