The metabolism of [¹⁴C]N-ethoxycarbonyl-3-morpholinosydnonimine (molsidomine) in man

Abstract

1. [¹⁴C]-N-Ethoxycarbonyl-3-morpholinosydnonimine (molsidomine, Corvaton®) was administered orally at a dose of 2 mg per subject to eight healthy male volunteers.

2. Maximal plasma concentrations of total radioactivity of 32.4±6.4ng equiv./ml (mean ± S.D.) were detected compared with maximum plasma concentrations of 141 ± 5.9ng/ml (mean±S.D.) of molsidomine. In both cases these were attained at 0.5 h after dosing. From the peak, concentrations of parent drug fell rapidly with a half-life of 1.25 ± 0.38 h (mean ± S.D.). In contrast, total radioactivity declined more slowly with a terminal half-life of 138 ± 42.7 h (mean ± S.D.).

3. The bulk of the radiolabel was rapidly excreted as metabolites in the urine, with over 85% of the dose recovered in the first 24 h. The main urinary radiolabelled metabolites appeared, from chromatographic evidence, to be similar to those previously identified in animals, namely N-morpholinosydnonimine, N-cyanomethylamino-N-(2'- hydroxyethy1)glycine and (N-cyanomethylenamino-2-aminoethyoxy)-acetic acid.