title: Comparison of plasma levels of canrenone and metabolites after base hydrolysis in young and elderly subjects following single and multiple doses of spironolactone.
abstract: Plasma levels of canrenone and 'total metabolites' after base hydrolysis were compared in young and elderly subjects following single and multiple doses of spironolactone. After the initial dose on Day 1, plasma levels of canrenone and 'total metabolites' were higher in the young than in the elderly group, and significant differences were found between the two age groups in the AUC for both canrenone and 'total metabolites'. However, these differences between the two age groups diminished after multiple dosing on Day 8, and the steady state pre-dose plasma levels of canrenone and 'total metabolites' were significantly higher in the elderly subjects. The accumulation ratios of canrenone and 'total metabolites' were significantly higher in the elderly than in the young subjects. Both canrenone and canrenoic acid were extensively bound to plasma protein, but no differences were found between the two age groups in protein binding. Observed differences in plasma levels after single and multiple dosing between young and old subjects may be consequences of many factors such as a proportionate shift in metabolism with age; impaired oral absorption of the parent compound; and/or altered volume of distribution of the drug.
mesh_terms: D000328:Adult; D000367:Age Factors; D000368:Aged; D001711:Biotransformation; D002192:Canrenone / Q000097:blood* / Q000378:metabolism; D005260:Female; D006801:Humans; D006868:Hydrolysis; D008297:Male; D008875:Middle Aged; D011245:Pregnadienes / Q000097:blood*; D011485:Protein Binding; D013050:Spectrometry, Fluorescence; D013148:Spironolactone / Q000008:administration & dosage*; D014462:Ultrafiltration
chemical_list: D011245:Pregnadienes; D013148:Spironolactone; D002192:Canrenone