Half-Life of Alprazolam (Xanax)
The half-life of 0.25mg Xanax (alprazolam) is approximately 11.2 hours in healthy adults, with a range of 6.3-26.9 hours. 1
Pharmacokinetic Profile of Alprazolam
Alprazolam is a triazolobenzodiazepine with the following pharmacokinetic properties:
- Absorption: Readily absorbed after oral administration
- Peak plasma concentration: Occurs in 1-2 hours following administration 1
- Distribution: 80% bound to human serum protein, primarily albumin 1
- Metabolism: Extensively metabolized by cytochrome P450 3A4 (CYP3A4) to two major metabolites:
- 4-hydroxyalprazolam
- α-hydroxyalprazolam
- Elimination: Primarily excreted in urine 1
Factors Affecting Alprazolam Half-Life
The half-life of alprazolam can vary significantly based on several patient factors:
- Age: Elderly patients have a longer mean half-life of 16.3 hours (range: 9.0-26.9 hours) compared to 11.0 hours in healthy adults 1
- Liver disease: In patients with alcoholic liver disease, half-life ranges between 5.8 and 65.3 hours (mean: 19.7 hours) 1
- Obesity: Obese individuals have a longer half-life ranging between 9.9 and 40.4 hours (mean: 21.8 hours) 1
- Race: Asians have approximately 25% longer half-life compared to Caucasians 1
- Smoking: Cigarette smoking may reduce alprazolam concentrations by up to 50% 1
Clinical Implications of Alprazolam's Half-Life
The 11.2-hour half-life of alprazolam places it in an intermediate category among benzodiazepines. This has several important clinical implications:
- It allows for less frequent dosing compared to shorter-acting benzodiazepines
- The drug may accumulate with repeated dosing, especially in patients with factors that prolong half-life
- Risk of withdrawal symptoms may be lower than with shorter-acting benzodiazepines but still present
Drug Interactions Affecting Half-Life
Several medications can significantly alter alprazolam's half-life through inhibition or induction of CYP3A4:
Inhibitors (increase alprazolam levels):
- Ketoconazole (increases AUC by 3.98-fold)
- Itraconazole (increases AUC by 2.70-fold)
- Cimetidine reduces clearance and increases half-life 2
Inducers (decrease alprazolam levels):
- Smoking may reduce concentrations by up to 50% 1
Practical Considerations
For the 0.25mg dose specifically, the same half-life applies as the elimination kinetics of alprazolam are dose-proportional within the therapeutic range. The low dose does not alter the fundamental pharmacokinetic properties, though it may reduce the risk of adverse effects compared to higher doses.
Understanding alprazolam's half-life is crucial for predicting:
- Duration of therapeutic effect
- Timing of potential withdrawal symptoms
- Risk of accumulation with repeated dosing
- Appropriate dosing intervals
This intermediate half-life makes alprazolam suitable for managing anxiety disorders while balancing efficacy and the risk of dependence.