Pharmacokinetics of Flosequinan and its Sulphone Metabolite in Asian Indians

Abstract

The pharmacokinetics of flosequinan, a peripheral vasodilator, and its active sulphone metabolite, flosequinoxan, were investigated in eleven Asian Indian male volunteers, in a phase 1 clinical trial. Flosequinan (50, 100 and 200 mg) and a randomized placebo dose was administered to volunteers, and blood samples were collected at frequent time intervals up to 96 h after dosing. Plasma was assayed for parent drug and metabolite by HPLC. While flosequinan exhibited linear pharmacokinetics and was rapidly eliminated with a mean elimination half-life (t½) of approximately 1.4 h, its metabolite, flosequinoxan, was eliminated very slowly, with a mean t½ of 25 h. Flosequinan underwent extensive first-pass metabolism to its sulphone metabolite, flosequinoxan.