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document
Pharmacokinetics and disposition of carvedilol in humans . Pharmacokinetics of carvedilol ( C ) have been studied in healthy volunteers after a single i.v . and oral administration , and the metabolic disposition after oral administration of 14C-labeled drug . C demonstrates dose-linear behavior . The absolute bioavailability reaches 24 % probably due to a first-pass effect . After a 50 mg oral dose , maximum concentrations of 66 micrograms/l are achieved within 1.2 h. C is extensively distributed to the tissues ( Vz = 132 l ) and eliminated primarily by hepatic metabolism ( total clearance 590 ml/min , renal clearance 4 ml/min ) . Because of the longer half-life of 6.4 h after oral administration in contrast to 2.4 h after i.v . administration , C is assumed to be absorption dependent since no sustained-release formulation was used . The half-life of radioactivity in plasma is 39 h ; 16 % of C is excreted in urine in the form of metabolites and only 0.3 % unchanged . The urinary metabolites consist of carvedilol glucuronide ( 5.2 % of the dose ) , cleavage products of the beta-blocking side chain ( 2.1 % ) , and ring-hydroxylated forms ( 2.9 % ) . Sixty percent of the dose is recovered in the feces . A demethylated product of C exhibits only minor beta-blocking activity . This metabolite is detected in plasma in concentrations ten times lower than the parent compound .
63923
Intervention_Pharmacological
carvedilol
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Intervention_Pharmacological
carvedilol
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Intervention_Pharmacological
14C-labeled drug
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Outcome_Other
Pharmacokinetics
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Outcome_Physical
half-life
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Outcome_Physical
beta-blocking activity
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Outcome_Physical
metabolite