PHARMACOKINETICS OF FLOSEQUINAN IN PATIENTS WITH HEART-FAILURE

Objective: The pharmacokinetics of flosequinan were studied in a group of 18 patients with chronic cardiac failure. Results: After a single dose of 100 mg, C-max of the parent compound (2.52 mg . l(-1)) was rec orded at 1.4 h, and of the sulphone metabolite flosequinoxan at 21.7 h . The plasma elimination half lives of the parent compound (6.4 h) and of the metabolite (54.3 h) were prolonged compared to previous studie s in normal volunteers. After repeated dose administration for 36 days , the kinetics of the parent compound and metabolite remained essentia lly unchanged with an expected significant accumulation of metabolite (C-max 8.4 vs 3.21 mg . l(-1)). No adverse effects were observed. Conc lusion: It is possible that altered drug kinetics in patients with hea rt failure, probably related to altered hepatic blood flow, could cont ribute to drug toxicity.