Clinical Pharmacokinetics and Pharmacodynamics of Carvedilol

Abstract

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.

Crystalline and amorphous carvedilol-loaded nanoemulsions: formulation optimisation using response surface methodology

“…Its solubility values are 51 mg mL À1 above pH 9.0, 23 mg mL À1 at pH 7 and about 100 mg mL À1 at pH 5 at room temperature [19]. Carvedilol undergoes significant stereoselective first-pass metabolism, resulting in low absolute bioavailability (30% or less) [20][21][22]. However, some sources suggest that this low bioavailability is the result of poor aqueous solubility [21,23].…”

Pharmacokinetic Drug Interaction between Carvedilol and Ticlopidine in Rats

“…Carvedilol is well absorbed from the gastrointestinal tract, but is subject to considerable first-pass metabolism in the intestinal and/or liver (McTavish et al, 1993;Morgan et al, 1994). Carvedilol is more than 98% bound to plasma proteins.…”

“…Carvedilol is metabolized by both oxidation and conjugation pathways in the liver into some metabolites (Neugebauer et al, 1987;Neugebauer and Neubert, 1991). The oxidation pathways are mainly catalyzed by CYP2C9 and CYP2D6 enzymes in human (McTavish and Neubert, 1993;Morgan, 1994;Oldham and Clarke, 1997), and then CYP2D6 is responsible for the formation of 4'-hydroxy carvedilol and 5'-hydroxy carvedilol, and both metabolites are excreted into urine (Neugebauer and Neubert, 1991). Carvedilol is also a substrate of P-gp (Bart and Neubert, 2005).…”

Evaluation of carvedilol-loaded microsponges with nanometric pores using response surface methodology

“…Its solubility is <1 mg/mL above pH 9.0, 23 mg/mL at pH 7, and about 100 mg/mL at pH 5 at room temperature [6]. Carvedilol undergoes significant stereoselective first-pass metabolism, resulting in low absolute bioavailability (30% or less) [7][8][9]. In this study, carvedilol was selected as a model drug for its suitability to be delivered through a microsponge-based drug delivery system.…”