Carvedilol: PHARMACOKINETICS

Carvedilol is a racemic mixture of two enantiomers. Its beta-blocking activity is the result of the S enantiomer, while its alpha-blocking activity is the result of both enantiomers .

Carvedilol is absorbed rapidly but undergoes a significant first-pass effect, resulting in a bioavailability of 25% to 35% . While administration with food may delay the time to peak concentration, the actual peak concentration and area under the concentration-time curve are not affected . The delay in absorption with food may be beneficial in decreasing the orthostatic hypotension that can be observed after carve-dilol administration.

Carvedilol is metabolized extensively by glucuronidation and oxidation, with less than 2% excreted unchanged in the urine . The cytochrome P450 isoenzymes that are primarily responsible for the oxidation of carvedilol are CYP2D6 and CYP2C9 . Because of this, carvedilol may be susceptible to several drug interactions (see ‘Drug Interactions’), and patients may exhibit genetic differences in the rate of drug metabolism. People who metabolize carvedilol poorly are expected to have higher concentrations of carvedilol than those who metabolize carvedilol extensively. (Metabolic status can be determined with debrisoquin or dextromethorphan, both of which are markers for the CYP2D6 enzyme.) It appears that the R(+) enantiomer demonstrates more genetic polymorphism and, therefore, alpha blockade may be more pronounced in people who metabolize carvedilol poorly. buy asthma inhalers

Carvedilol is highly protein-bound (95%), primarily to albumin . Carvedilol is also very lipid soluble and is expected to cross the blood-brain barrier, causing central nervous system effects similar to those seen with other beta-blockers. Animal studies have demonstrated low placental transfer, but excretion of carvedilol into breast milk is evident.

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