The metabolism and excretion of (+)-[¹⁴C]cyanidanol-3 in man following oral administration

Abstract

1. Following administration of a single dose of [U¹⁴C]cyanidanol-3 to human volunteers, a mean of 55% of the dose of ¹⁴C was excreted in urine; 90% of urine ¹⁴C was excreted within 24 h of drug administration.

2. The major urinary metabolites were the glucuronides of (+)-catechin and 3′-O-methyl-(+)-catechin, and the sulphate of the latter. These three conjugates collectively accounted for three quarters of urine ¹⁴C. Urinary excretion of unchanged (+)-cyanidanol-3 was 0.1–1.4% dose.

3. (+)-Cyanidanol-3 and metabolites containing the intact flavanol ring system accounted for 90% of urine ¹⁴C. Ring scission was, under these conditions, a minor metabolic pathway resulting in the excretion of small amounts of 3-hydroxybenzoic acid, 3-hydroxyhippuric acid and 3-hydroxyphenylpropionic acid.

4. Unchanged (+)-cyanidanol-3 was detected in plasma between 30 min and 12h after administration. Metabolites (as total ¹⁴C) persisted in plasma for at least 120h after administration.