What is the half-life of alprazolam (Xanax)?

Alprazolam Half-Life

The elimination half-life of alprazolam is approximately 11.2 hours (range: 6.3–26.9 hours) in healthy adults, according to FDA labeling. 1

Standard Pharmacokinetic Parameters

• Mean half-life in healthy adults: 11.2 hours with a documented range of 6.3 to 26.9 hours 1
• Peak plasma concentrations occur 1 to 2 hours following oral administration 1
• Alprazolam is extensively metabolized primarily by cytochrome P450 3A4 (CYP3A4) 1
• The drug demonstrates approximately 80-100% oral bioavailability 2

Special Population Considerations

Elderly Patients

• 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 elimination increases risk of drug accumulation and adverse effects in geriatric populations 1

Hepatic Impairment

• Patients with alcoholic liver disease show markedly prolonged half-life: mean 19.7 hours (range: 5.8–65.3 hours) compared to 11.4 hours in healthy subjects 1
• Clearance is significantly reduced in cirrhosis 2

Obesity

• Obese patients demonstrate extended half-life: mean 21.8 hours (range: 9.9–40.4 hours) versus 10.6 hours in non-obese subjects 1

Racial Differences

• Asian populations show approximately 25% higher half-life compared to Caucasians 1
• Maximal concentrations are also approximately 15% higher in Asians 1

Clinical Implications

• The intermediate half-life allows for twice or three times daily dosing in most patients 3
• At steady state, mean plasma concentrations change by 10-12 micrograms/L for each 1 mg/day dosage adjustment 2
• Pharmacokinetics are dose-independent and unchanged during multiple-dose treatment 2
• The metabolites (4-hydroxyalprazolam and α-hydroxyalprazolam) have similar half-lives but appear at concentrations less than 4% of parent drug and are unlikely to contribute significantly to pharmacological effects 1

Important Drug Interactions Affecting Half-Life

CYP3A4 Inhibitors (Prolong Half-Life)

• Ketoconazole increases alprazolam AUC by 3.98-fold 1
• Itraconazole increases AUC by 2.70-fold 1
• Nefazodone increases AUC by 1.98-fold 1
• Fluvoxamine increases AUC by 1.96-fold 1
• Cimetidine and oral contraceptives reduce clearance and increase half-life 4

CYP3A4 Inducers (Shorten Half-Life)

• Carbamazepine (300 mg/day for 10 days) shortened half-life from 17.1 hours to 7.7 hours and increased oral clearance from 0.90 to 2.13 mL/min/kg 1

Factors NOT Affecting Half-Life

• Gender has no effect on pharmacokinetics 1
• Renal disease does not significantly alter half-life, though it reduces plasma protein binding 2
• Abstinent alcoholics show no significant pharmacokinetic changes 2
• Phase of menstrual cycle does not influence pharmacokinetics 2

Common Pitfall

Cigarette smoking reduces alprazolam concentrations by up to 50% compared to non-smokers, which may necessitate dosage adjustments 1. This is a frequently overlooked factor that can lead to apparent treatment failure.