Pharmacokinetics of molsidomine in humans.

The pharmacokinetics of molsidomine were investigated in the plasma and urine of healthy male volunteers and patients with coronary heart disease after intravenous and/or oral administration of different galenic dosage forms of molsidomine. Following the rapid attainment of mean peak concentration (15 +/- 7 mg/ml) 0.5 to 1.0 hour after single oral dosing of 2 mg of molsidomine, the plasma levels of the unchanged drug decline monoexponentially with a mean half-life of 1.6 +/- 0.8 hours. Molsidomine is absorbed almost completely. Its absolute bioavailability (44 +/- 15%) and a 14C-labeled triale give evidence of quick biotransformation of molsidomine to active metabolites. Less than 2% of the unchanged drug appear in the urine, but renal excretion is the main route of elimination of the metabolites in humans (90% to 95%). The kinetics parameters after administration of multiple dosages of 4 mg of molsidomine over 29 days do not account for accumulation of or enzyme induction by molsidomine. The finding of obvious good correlations between plasma levels of the predrug molsidomine and corresponding pharmacodynamic data can be made plausible by the time course of concentration values of the active metabolite SIN-1 in plasma.