Liver function and pharmacokinetics of molsidomine and its metabolite 3-morpholinosydnonimine in healthy volunteers

Abstract

Plasma levels of N-carboxy-3-morpholinosydnonimine ethyl ester (molsidomine, Corvaton) and its pharmacologically active metabolite 3-morpholinosydnonimine (SIN-1) were measured in six healthy male and female volunteers after single intravenous and oral dosing of 4 mg molsidomine. Additionally indocyanine green and phenazone (antipyrine) clearances were determined to estimate hepatic blood flow and metabolic liver function in each subject. The pharmacokinetic parameters of molsidomine were similar to already published data in healthy volunteers and patients. The plasma level of SIN-1 formed was always lower than the molsidomine level but obviously reflects the corresponding molsidomine concentration time course in plasma. Indocyanine green plasma clearance was reduced by 15%. after intravenous dosing of 4 mg molsidomine. There was no clear-cut relationship between the plasma clearances of molsidomine and phenazone in these subjects with normal metabolic liver function.