Single intravenous and oral doses of fenflumizole: pharmacokinetics and effects on prostanoid formation.
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.
D015121:6-Ketoprostaglandin F1 alpha / Q000096:biosynthesis; D000284:Administration, Oral; D000328:Adult; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage* / Q000378:metabolism / Q000494:pharmacology; D001682:Biological Availability; D006801:Humans; D007093:Imidazoles / Q000008:administration & dosage* / Q000378:metabolism / Q000494:pharmacology; D007275:Injections, Intravenous; D007700:Kinetics; D008297:Male; D008657:Metabolic Clearance Rate; D011453:Prostaglandins / Q000096:biosynthesis*; D013929:Thromboxane B2 / Q000096:biosynthesis
D000893:Anti-Inflammatory Agents; D007093:Imidazoles; D011453:Prostaglandins; D013929:Thromboxane B2; D015121:6-Ketoprostaglandin F1 alpha; C038996:fenflumizole