ADMET-Absorption, Distribution, Metabolism, Excretion, and Toxicity

StatusFDA approved
AdministrationN/A
PharmacologyA non-selective beta blocker/alpha-1 blocker indicated in the treatment of mild to moderate congestive heart failure (CHF).

Absorption_value80.0
Absorption (description)Carvedilol is rapidly and well absorbed after oral administration, but is subject to considerable first-pass metabolism in the liver.
Caco_2N/A
Bioavailability25.0

MetabollsmThe drug is widely distributed and extensively metabolised, primarily by aromatic ring oxidation and glucuronidation. The oxidative metabolites undergo further metabolism by glucuronidation and sulfation. Some of the metabolites have beta-blocking and vasodilating activity; one metabolite has greater beta-blocking activity than carvedilol but all have weaker vasodilating effects than carvedilol. The o-demethyl-p-hydroxyl and m-hydroxyl metabolites possess beta-blocking activity. Its metabolism is stereoselective and plasma concentrations of R(+)-carvedilol are about 2 to 3 times higher than S(??)-carvedilol. The principal enzymes involved are CYP2D6 and CYP2C9. The metabolism of carvedilol is subject to genetic polymorphism with poor metabolisers of debrisoquine having plasma-R(+)-carvedilol concentrations 2- to 3-fold higher than extensive metabolisers. It is not significantly cleared by haemodialysis. No accumulation of the drug has been observed.
Half life2.2 h

ExcretionThe metabolites are excreted mainly via bile into faeces. Approximately 16% of a dose is detected in urine with less than 2% as the unchanged drug.
Urinary Excretion<2
Clerance8.7 ml/min/kg