Pharmacokinetics and metabolism of mespirenone, a new aldosterone antagonist, in rat and cynomolgus monkey.
The pharmacokinetics and metabolism of mespirenone were examined in rat and cynomolgus monkey using the tritiated drug. Following i.v. administration, mespirenone exhibited a short half-life and a high plasma clearance; after oral administration the unchanged compound was not detectable. Thus, mespirenone has to be considered a pro-drug. From rat urine three metabolites were isolated by h.p.l.c. and identified by mass spectra and 1H n.m.r., all having retained the 7 alpha-sulphur substituent as a thiomethyl or a sulphinylmethyl group. The 7 alpha-thiomethyl metabolite had a half-life of six hours in rat plasma and its AUC value was 35% of that for total 3H. As this metabolite has marked anti-aldosterone activity, it is an active metabolite that contributes to the pharmacological effect of mespirenone.
D000284:Administration, Oral; D000818:Animals; D001711:Biotransformation; D005260:Female; D006207:Half-Life; D007275:Injections, Intravenous; D007700:Kinetics; D008252:Macaca fascicularis; D000451:Mineralocorticoid Receptor Antagonists / Q000008:administration & dosage / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D013045:Species Specificity; D013148:Spironolactone / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000378:metabolism; D014018:Tissue Distribution
D000451:Mineralocorticoid Receptor Antagonists; D013148:Spironolactone; C051308:mespirenone