Half-Life of Xanax (Alprazolam)
The elimination half-life of alprazolam (Xanax) in healthy adults is approximately 11.2 hours, with a range of 6.3 to 26.9 hours. 1
Pharmacokinetic Profile
- Peak plasma concentrations occur 1 to 2 hours following oral administration 1
- Absorption is rapid and nearly complete, with absolute bioavailability averaging 80-100% 2
- Plasma protein binding is approximately 80%, primarily to serum albumin 1
- Metabolism occurs primarily via hepatic cytochrome P450 3A4 (CYP3A4) to two major metabolites: 4-hydroxyalprazolam and α-hydroxyalprazolam, both of which have minimal pharmacological activity 1
Half-Life Variations in Special Populations
Elderly Patients
- Mean half-life increases to 16.3 hours (range: 9.0-26.9 hours) in healthy elderly subjects compared to 11.0 hours in younger adults 1
- This prolonged half-life necessitates dose reduction of 50% or more in elderly patients 3
Hepatic Impairment
- Half-life ranges from 5.8 to 65.3 hours (mean: 19.7 hours) in patients with alcoholic liver disease, compared to 6.3-26.9 hours in healthy subjects 1
- Clearance is significantly reduced in cirrhosis, requiring lower starting doses 2
Obesity
- Half-life ranges from 9.9 to 40.4 hours (mean: 21.8 hours) in obese patients, compared to 6.3-15.8 hours in normal-weight subjects 1
Asian Populations
- Half-life is approximately 25% higher in Asians compared to Caucasians 1
Smokers
- Alprazolam concentrations may be reduced by up to 50% in smokers compared to non-smokers, effectively shortening the clinical duration of action 1
Clinical Implications of Half-Life
- The 11-hour half-life requires multiple daily doses (typically 2-3 times daily) to maintain therapeutic plasma concentrations throughout the day 2, 4
- Steady-state is achieved in approximately 2-3 days (approximately 5 half-lives) with regular dosing 2
- The relatively short half-life compared to longer-acting benzodiazepines like diazepam means less drug accumulation but also higher risk of interdose withdrawal symptoms 2
Common Pitfalls
- Do not assume consistent half-life across all patients: The wide range (6.3-26.9 hours) means some patients may require more frequent dosing while others accumulate drug with standard regimens 1
- Drug interactions significantly alter half-life: Cimetidine, fluoxetine, and fluvoxamine significantly impair alprazolam clearance and prolong half-life, requiring dose adjustments 2, 5
- Renal disease increases free fraction due to reduced plasma protein binding, though total clearance may be less affected than with hepatic disease 2