What is the half-life of nebivolol?

Half-Life of Nebivolol

The half-life of nebivolol is approximately 12 hours in extensive metabolizers (most people) and approximately 19 hours in poor metabolizers of CYP2D6. 1

Pharmacokinetic Profile

Nebivolol is a highly selective beta-1 adrenergic receptor blocker with unique vasodilatory properties. Its pharmacokinetic profile is characterized by:

• Metabolism: Primarily through the CYP2D6 enzyme system 1
• Genetic variation: Significant differences exist between:
  • Extensive metabolizers (90% of population): 12-hour half-life
  • Poor metabolizers (10% of population): 19-hour half-life 1, 2
• Absorption: Rapid absorption with peak plasma concentrations occurring at 0.5-2 hours post-dose 2
• Bioavailability: High lipophilicity contributes to its absorption profile 2
• Excretion: Less than 0.5% of unchanged nebivolol is excreted in urine or feces 2

Clinical Implications of Nebivolol's Half-Life

The 12-hour half-life in most patients supports the standard twice-daily dosing regimen for optimal therapeutic effect. This provides several clinical advantages:

• Steady plasma levels: The half-life allows for relatively stable drug concentrations throughout the day
• Consistent beta-blockade: Maintains therapeutic effect between doses
• Dosing considerations:
  • For patients with renal impairment: Clearance is reduced by 53% in severe renal impairment 1
  • For patients with hepatic impairment: Exposure (AUC) increases 10-fold in moderate hepatic impairment 1

Special Populations

Several patient factors can affect nebivolol's half-life:

• Hepatic impairment: In patients with moderate hepatic impairment (Child-Pugh Class B), the apparent clearance decreases by 86% 1
• Renal impairment:
  • Mild to moderate impairment: Minimal effect on clearance
  • Severe impairment (CrCl <30 mL/min): Clearance reduced by 53% 1
• Obesity: Higher clearance (71.6 L/h vs 51.6 L/h in normal weight individuals) but similar half-life 3

Stereoisomer Considerations

Nebivolol exists as a racemic mixture of d- and l-enantiomers:

• The d-isomer (d-nebivolol) has >1000-fold higher beta-receptor affinity than l-nebivolol 1
• The l-isomer's pharmacokinetics are more affected by CYP2D6 metabolizer status than the d-isomer 3

The 12-hour half-life of nebivolol in most patients provides an optimal pharmacokinetic profile for clinical use in hypertension and other cardiovascular conditions, balancing efficacy with a convenient dosing schedule.