Pharmacokinetics of Enoximone After Various Intravenous Administrations to Healthy Volunteers

Abstract

The pharmacokinetics of enoximone and its sulfoxide metabolite were investigated in healthy male volunteers after various intravenous adminstrations: a bolus single dose, a continuous infusion, and bolus multiple doses of enoximone. The overall pharmacokinetic profiles of enoximone and sulfoxide metabolite indicated linearity over the range of 0.25–2.0 mg/kg after single doses of enoximone. The hypothetical plasma concentration just after bolus injection of enoximone, the maximum concentration of sulfoxide, and the area under the concentration–time curves of both compounds increased proportionally with dose. The terminal half‐lives of both compounds indicated similar values (2.0–2.7 h) and were not dose related. After four consecutive doses given at 3‐h intervals, no accumulation was observed for either compound, and the pharmacokinetic parameters were not altered. After a 4‐h infusion of enoximone, the areas under the plasma concentration–time curves of both compounds were 30% lower than the estimated values from the single dose study. Also, some pharmacokinetic parameters were changed as compared to those from the single dose study. The pharmacokinetic parameters obtained in Japanese healthy volunteers showed no marked differences from those obtained in Caucasians; thus, no racial difference was suggested in the pharmacokinetic properties of enoximone.