Half-Life Comparison: Xanax vs Ativan
Xanax (alprazolam) has a mean half-life of approximately 11.2 hours (range 6.3-26.9 hours), while Ativan (lorazepam) has a mean half-life of approximately 12 hours for the parent compound and 18 hours for its major metabolite (lorazepam glucuronide). 1, 2
Detailed Pharmacokinetic Profiles
Alprazolam (Xanax)
- The elimination half-life averages 11.2 hours in healthy adults, with a range of 6.3 to 26.9 hours 1
- Peak plasma concentrations occur 1-2 hours after oral administration 1
- The half-life increases to approximately 16.3 hours in elderly patients (range 9.0-26.9 hours) compared to 11.0 hours in younger adults 1
- In patients with alcoholic liver disease, the half-life ranges from 5.8 to 65.3 hours (mean 19.7 hours) 1
- In obese patients, the half-life ranges from 9.9 to 40.4 hours (mean 21.8 hours) 1
- Alprazolam is extensively metabolized by CYP3A4 to two major metabolites (4-hydroxyalprazolam and α-hydroxyalprazolam), which are essentially inactive and present at very low concentrations 1
Lorazepam (Ativan)
- The mean half-life of unconjugated lorazepam is approximately 12 hours in human plasma 2
- The major metabolite, lorazepam glucuronide, has a half-life of approximately 18 hours 2
- Peak plasma concentrations occur approximately 2 hours after oral administration 2
- Lorazepam has an intermediate half-life of 8-15 hours with no active metabolites, making it safer in renal failure cases 3
- Advancing age does not significantly affect lorazepam pharmacokinetics, though one study showed a 20% decrease in total body clearance in elderly patients (60-84 years) compared to younger subjects 2
- Lorazepam is rapidly conjugated into lorazepam glucuronide, which has no demonstrable CNS activity 2
Clinical Implications of Half-Life Differences
Duration of Action
- Lorazepam provides more prolonged clinical effects, with sedative effects persisting more than 240 minutes after oral dosing and anticonvulsant activity lasting up to 72 hours in seizure management 4
- Alprazolam's shorter half-life may lead to withdrawal symptoms between doses, particularly in patients taking it multiple times daily 3
- The clinical effect and amnesia begin more rapidly with diazepam than lorazepam, but last longer following lorazepam 5
Metabolic Considerations
- Lorazepam is preferred in patients with hepatic or renal dysfunction because it undergoes simple glucuronide conjugation and has no active metabolites 3, 2
- Alprazolam is metabolized via CYP3A4, making it subject to numerous drug interactions with CYP3A4 inhibitors and inducers 1
- Lorazepam's lack of active metabolites provides more predictable effects and easier dose titration 4
Special Populations
- In elderly patients, alprazolam's half-life increases by approximately 48% (from 11.0 to 16.3 hours), while lorazepam shows minimal age-related changes 1, 2
- Alprazolam concentrations may be reduced by up to 50% in smokers compared to non-smokers 1
- Asian patients have approximately 25% higher half-life values for alprazolam compared to Caucasians 1
Clinical Selection Guidance
When to Choose Lorazepam
- Lorazepam is preferred for acute agitation due to its rapid onset, complete absorption, and lack of active metabolites 3
- Patients with hepatic or renal impairment benefit from lorazepam's simpler metabolism 3, 2
- When predictable duration and easier dose titration are priorities 4
When to Consider Alprazolam
- Alprazolam is primarily indicated for anxiety disorders, particularly panic disorder 3
- The slightly shorter half-life may reduce accumulation risk with multiple daily dosing in some patients 1
Critical Warnings
- Both medications cause dose-dependent respiratory depression, especially when combined with opioids or alcohol 3, 6
- Parenteral lorazepam contains propylene glycol, which can cause metabolic acidosis and acute kidney injury at doses as low as 1 mg/kg/day 6
- Long-term use of either medication leads to tolerance, physical dependence, and withdrawal symptoms upon cessation 3, 7