Absorption, distribution and elimination of felodipine in man

The objectives of these investigations were to study the absorption and disposition characteristics of felodipine in young healthy male volunteers following acute administration of different intravenous and oral doses, and to study urinary metabolites of [14C]felodipine following oral administration. Felodipine is rapidly and extensively absorbed from the gastrointestinal tract but owing to presystemic elimination, probably primarily in the liver, only 15% on average is systemically available. The systemic availability is independent of the oral dose in the 5 to 40 mg dose interval. The major fraction of the felodipine dose is localised extravascularly with a volume of distribution of about 10 L/kg. Less than 1% is confined to the blood. Felodipine is extensively bound to plasma proteins (greater than 99%). The mean elimination half-life of felodipine is greater than 10 hours. The urinary metabolic pattern of felodipine, using high pressure liquid chromatography, reveals 3 major metabolites (carboxylic acids of oxidised felodipine) in human urine.