Nebivolol: pharmacologic profile of an ultraselective, vasodilatory beta1-blocker.
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 beta(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 beta-blockers. Nebivolol is thus a novel beta-blocker with several important pharmacologic properties that distinguish it from traditional beta-blockers. These unique properties may confer clinical benefits beyond simple blood pressure lowering.
Prisant
L Michael
LM
Hypertension and Clinical Pharmacology, Medical College of Georgia, 1467 Harper Street, HB 2010, Augusta, GA 30912, USA. mprisant@mcg.edu
D058671:Adrenergic beta-1 Receptor Antagonists; D000319:Adrenergic beta-Antagonists / Q000737:chemistry / Q000494:pharmacology*; D000818:Animals; D000975:Antioxidants / Q000737:chemistry / Q000494:pharmacology; D001578:Benzopyrans / Q000737:chemistry / Q000494:pharmacology*; D004983:Ethanolamines / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D015394:Molecular Structure; D000068577:Nebivolol; D010975:Platelet Aggregation Inhibitors / Q000737:chemistry / Q000494:pharmacology; D013237:Stereoisomerism; D014665:Vasodilator Agents / Q000737:chemistry / Q000494:pharmacology*
D058671:Adrenergic beta-1 Receptor Antagonists; D000319:Adrenergic beta-Antagonists; D000975:Antioxidants; D001578:Benzopyrans; D004983:Ethanolamines; D010975:Platelet Aggregation Inhibitors; D014665:Vasodilator Agents; D000068577:Nebivolol