On the pharmacokinetics of fenflumizole, a novel antiinflammatory agent, after single oral administration to healthy subjects.

: The disposition of fenflumizole, a recently developed imidazole derivative which inhibits prostanoid formation, was studied after single oral administration to eight 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 hrs were amenable to a two-compartment open model and showed a rapid absorption with a half-life of about 0.5 hr and peak concentrations in plasma after about 1 hr. The elimination phase became dominating after about 10 hrs with a half-life of 14–15 hrs. 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 hrs no dose-dependent bioavailability was revealed. The mean transit time in plasma ranged from 21 to 22 hrs. Two metabolites (demethylation products) were detected in both plasma and urine. Their plasma concentrations amounted to only about 5% of those of the parent compound, and they were rapidly eliminated. The total urinary recovery of the intact fenflumizole and the two metabolites was less than 0.1%0 of the given doses. The renal clearance of fenflumizole was estimated to about 0.02 ml/hr.