Nebivolol: Pharmacologic Profile of an Ultraselective, Vasodilatory ₁-Blocker

¹ Medical College of Georgia

^* To whom correspondence should be addressed. E-mail: mprisant{at}mail.mcg.edu.

	Abstract

Beta-blockers are well-established therapeutic agents in the treatment of hypertension and cardiovascular disease. However, these agents are highly heterogeneous. Beta-blockers differ in their ancillary pharmacologic properties, which are clinically important. Nebivolol is a highly selective ₁-adrenergic receptor blocker that induces vasodilation through stimulation of the endothelial nitric oxide/L-arginine pathway. As a racemic mixture of d- and l-enantiomers, nebivolol is highly lipophilic and rapidly absorbed. Nebivolol undergoes extensive hepatic metabolism through the cytochrome P450 2D6 (CYP2D6) system. As a result of genetic polymorphisms, CYP2D6 has variable activity, manifested by extensive and poor metabolizers of nebivolol. Time to maximum concentration is 0.5 to 2 hours, and half-life is 11 hours in extensive metabolizers; these values are about 3 times longer in poor metabolizers. Urinary and fecal excretion of unchanged nebivolol is less than 0.5% of the dose. Nebivolol has a unique hemodynamic profile of reduced systemic vascular resistance and increased left ventricular function. These properties are attributed to its vasodilating action and contrast with the hemodynamic effects of conventional -blockers. Nebivolol is thus a novel -blocker with several important pharmacologic properties that distinguish it from traditional -blockers. These unique properties may confer clinical benefits beyond simple blood pressure lowering.
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