Clinical pharmacokinetics and pharmacodynamics of carvedilol.

Carvedilol is an arylethanolamine that is a racemic mixture of 2 enantiomers. The S-(-)-enantiomer has beta-adrenoceptor blocking activity, while the racemate also has alpha 1-receptor blocking activity due to the activity of the R-(+)-enantiomer. The drug is rapidly absorbed and undergoes extensive first-pass metabolism in the liver. It reaches a peak concentration 1 to 2 hours postdose and has an elimination half-life of about 4 to 7 hours. Absorption is delayed by food. The drug is highly lipophilic and is highly protein bound. The drug is metabolised by the liver, with some metabolites having biological activity. The pharmacokinetic profile is not altered in the elderly or in patients with renal disease. However, bioavailability of the oral medication is greatly increased in patients with liver disease. Carvedilol lowers blood pressure as a result of its beta-blocking and vasodilatory activity. The reduction in blood pressure is similar to that achieved with other antihypertensive drugs, and there are no adverse effects on renal or cerebral blood flow. Carvedilol has been used in small numbers of patients with cardiac failure. It reduces left ventricular hypertrophy and has no significant adverse metabolic effects.