On the Pharmacokinetics of Fenflumizole, a Novel Antiinflammatory Agent, after Single Oral Administration to Healthy Subjects

Publisher Website
Google Scholar
Abstract
The disposition of fenflumizole, a recently developed imidazole derivative which inhibits prostanoid formation, was studied after single oral administration to 8 healthy subjects. Fenflumizole was given in the doses 0.1, 1 and 2 mg/kg as an aqueous suspension. Plasma concentrations within the first 24 h were amenable to a 2-compartment open model and showed a rapid absorption with a half-life of about 0.5 h and peak concentrations in plasma after .apprx. 1 h. The elimination phase became dominating after about 10 h with a half-life of 14-15 h. Peak plasma levels and areas under the concentration-time curves prior to onset of the elimination phase indicated a small reduction of the bioavailability with dose on comparison of the highest and the lowest dose (P < 0.05) but for the whole observation period of 24 h no dose-dependent bioavailability was revealed. The mean transit time in plasma ranged from 21-22 h. Two metabolites (demethylation products) were detected in both plasma and urine. Their plasma concentrations amounted to only .apprx. 5% of those of the parent compound and they were rapidly eliminated. The total urinary recovery of the intact fenflumizole and the 2 metabolites was < 0.1.permill. of the given doses. The renal clearance of fenflumizole was estimated to .apprx. 0.02 ml/h.