Nebivolol - How It Works
Clinical pharmacology details from the US FDA-approved label: how Nebivolol works in your body, how it's absorbed, how long it stays active, and how it's eliminated.
Mechanism of Action
12.1 Mechanism of Action The mechanism of action of the antihypertensive response of nebivolol tablets has not been definitively established. Possible factors that may be involved include: decreased heart rate, decreased myocardial contractility, diminution of tonic sympathetic outflow to the periphery from cerebral vasomotor centers, suppression of renin activity and vasodilation and decreased peripheral vascular resistance.
CLINICAL PHARMACOLOGY Nebivolol is a β-adrenergic receptor blocking agent.
In extensive metabolizers (most of the population) and at doses less than or equal to 10 mg, nebivolol is preferentially β 1 selective.
In poor metabolizers and at higher doses, nebivolol inhibits both β 1 -and β 2 -adrenergic receptors.
Nebivolol lacks intrinsic sympathomimetic and membrane stabilizing activity at therapeutically relevant concentrations.
At clinically relevant doses, nebivolol tablets do not demonstrate α 1 -adrenergic receptor blockade activity.
Various metabolites, including glucuronides, contribute to β-blocking activity.
12.1 Mechanism of Action The mechanism of action of the antihypertensive response of nebivolol tablets has not been definitively established.
Possible factors that may be involved include: decreased heart rate, decreased myocardial contractility, diminution of tonic sympathetic outflow to the periphery from cerebral vasomotor centers, suppression of renin activity and vasodilation and decreased peripheral vascular resistance.
12.3 Pharmacokinetics Nebivolol is metabolized by a number of routes, including glucuronidation and hydroxylation by CYP2D6.
The active isomer (d-nebivolol) has an effective half-life of about 12 hours in CYP2D6 extensive metabolizers (most people), and 19 hours in poor metabolizers and exposure to d-nebivolol is substantially increased in poor metabolizers.
This has less importance than usual, however, because the metabolites, including the hydroxyl metabolite and glucuronides (the predominant circulating metabolites), contribute to β-blocking activity.
Plasma levels of d–nebivolol increase in proportion to dose in EMs and PMs for doses up to 20mg.
Exposure to l-nebivolol is higher than to d-nebivolol but l-nebivolol contributes little to the drug’s activity as d-nebivolol’s beta receptor affinity is > 1000-fold higher than l-nebivolol.
For the same dose, PMs attain a 5-fold higher C max and 10-fold higher AUC of d-nebivolol than do EMs. d-Nebivolol accumulates about 1.5-fold with repeated once-daily dosing in EMs.
Absorption Absorption of nebivolol tablets is similar to an oral solution.
The absolute bioavailability has not been determined.
Mean peak plasma nebivolol concentrations occur approximately 1.5 to 4 hours post-dosing in EMs and PMs.
Food does not alter the pharmacokinetics of nebivolol.
Under fed conditions, nebivolol glucuronides are slightly reduced.
Nebivolol tablets may be administered without regard to meals.
Pharmacokinetics
12.3 Pharmacokinetics Nebivolol is metabolized by a number of routes, including glucuronidation and hydroxylation by CYP2D6. The active isomer (d-nebivolol) has an effective half-life of about 12 hours in CYP2D6 extensive metabolizers (most people), and 19 hours in poor metabolizers and exposure to d-nebivolol is substantially increased in poor metabolizers. This has less importance than usual, however, because the metabolites, including the hydroxyl metabolite and glucuronides (the predominant circulating metabolites), contribute to β-blocking activity. Plasma levels of d–nebivolol increase in proportion to dose in EMs and PMs for doses up to 20mg. Exposure to l-nebivolol is higher than to d-nebivolol but l-nebivolol contributes little to the drug’s activity as d-nebivolol’s beta receptor affinity is > 1000-fold higher than l-nebivolol. For the same dose, PMs attain a 5-fold higher C max and 10-fold higher AUC of d-nebivolol than do EMs. d-Nebivolol accumulates about 1.5-fold with repeated once-daily dosing in EMs. Absorption Absorption of nebivolol tablets is similar to an oral solution. The absolute bioavailability has not been determined. Mean peak plasma nebivolol concentrations occur approximately 1.5 to 4 hours post-dosing in EMs and PMs. Food does not alter the pharmacokinetics of nebivolol. Under fed conditions, nebivolol glucuronides are slightly reduced. Nebivolol tablets may be administered without regard to meals. Distribution The in vitro human plasma protein bi