What is the half-life of nebivolol in an adult patient with hypertension?

Half-Life of Nebivolol

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

Pharmacokinetic Details

Standard Population (Extensive Metabolizers)

• The active d-nebivolol enantiomer has an effective half-life of about 12 hours in CYP2D6 extensive metabolizers, who represent the majority of patients. 1
• Time to maximum plasma concentration occurs approximately 1.5 to 4 hours after dosing. 1
• The drug accumulates approximately 1.5-fold with repeated once-daily dosing in extensive metabolizers. 1

Poor Metabolizers

• In CYP2D6 poor metabolizers, the half-life extends to approximately 19 hours. 1
• Poor metabolizers achieve 5-fold higher peak concentrations (Cmax) and 10-fold higher overall drug exposure (AUC) of d-nebivolol compared to extensive metabolizers. 1
• One study reported even longer half-lives of 32-34 hours in poor hydroxylators. 2

Clinical Implications

Dosing Considerations

• Despite the pharmacokinetic differences between extensive and poor metabolizers, the clinical impact is less pronounced than expected because active metabolites (including hydroxyl metabolites and glucuronides) contribute significantly to the overall β-blocking activity. 1
• The once-daily dosing regimen remains appropriate for both metabolizer phenotypes due to the contribution of active metabolites. 1, 3

Metabolism and Excretion

• Nebivolol undergoes extensive hepatic metabolism primarily through CYP2D6-mediated hydroxylation and direct glucuronidation. 1
• After oral administration, 38% of the dose is recovered in urine and 44% in feces in extensive metabolizers, while poor metabolizers excrete 67% in urine and 13% in feces. 1
• Essentially all nebivolol is excreted as oxidative metabolites or their glucuronide conjugates, with less than 0.5% excreted unchanged. 1, 3

Special Populations

• In patients with moderate hepatic impairment (Child-Pugh Class B), drug exposure increases 10-fold and apparent clearance decreases by 86%, necessitating dose adjustment. 1
• In severe renal impairment (creatinine clearance <30 mL/min), clearance is reduced by 53%. 1
• In chronic kidney disease patients, the AUC is approximately 3-fold greater than in healthy individuals. 4

Important Caveats

Drug Interactions Affecting Half-Life

• Co-administration with CYP2D6 inhibitors (bupropion, duloxetine, fluvoxamine, paroxetine, fluoxetine) significantly increases nebivolol's Cmax, AUC, and half-life. 4
• These interactions can effectively convert extensive metabolizers into poor metabolizer phenotypes, prolonging drug exposure. 4

Overdose Management

• In overdose situations, hemodialysis is not expected to enhance nebivolol clearance due to extensive drug binding to plasma proteins (approximately 98%). 1
• The 12-19 hour half-life should guide the duration of monitoring and supportive care in overdose cases. 1