Metabolism of [14C] felodipine, a new vasodilating drug, in healthy volunteers.

After oral administration of [14C] felodipine (27.5mg) to 4 healthy volunteers, 6 main urinary metabolites were identified by gas chromatography-mass spectrometry. The compounds were isolated by solvent extraction at pH 2.2 and silylated prior to analysis. They were formed by dehydrogenation of felodipine followed by ester hydrolysis, hydroxylation of the alkyl groups and conjugation. These metabolites were excreted both as free acids and as conjugates accounting on average for 37% of the excreted amount (23% of the dose). A specific liquid chromatographic assay with radioactive detection was developed to determine the acidic metabolites in all collected samples. The urinary excretion rate declined biphasically for the mono-acids III and IV, whereas the excretion rates of metabolites VI, VII and VIII, formed via aliphatic hydroxylation, were better fitted to equations of first-order processes.