Half-Life of Lorazepam 0.5 mg Tablet
The elimination half-life of lorazepam is approximately 12 hours in adults, regardless of the dose (whether 0.5 mg or any other strength), as the pharmacokinetics are dose-proportional. 1
Pharmacokinetic Profile
The half-life of lorazepam remains consistent across different doses because plasma levels are directly proportional to the dose administered, without evidence of accumulation during chronic use up to 6 months. 1
- Peak plasma concentration occurs approximately 2 hours after oral administration 1, 2
- Absorption is rapid with 90% absolute bioavailability and a first-order absorption half-life of approximately 15 minutes 1, 2
- Elimination half-life is approximately 12 hours for unconjugated lorazepam 1, 3, 2
- Metabolite half-life (lorazepam glucuronide) is approximately 18 hours, though this metabolite has no CNS activity 1
Metabolism and Clearance
Lorazepam undergoes simple glucuronidation rather than oxidative metabolism, which distinguishes it from many other benzodiazepines. 3, 2
- Primary metabolic pathway: Direct conjugation with glucuronic acid at the 3-hydroxy group to form inactive lorazepam glucuronide 1, 2
- Urinary excretion: 86-88% of the administered dose is recovered in urine as the glucuronide conjugate 3, 2
- Protein binding: Approximately 85% bound to plasma proteins at clinically relevant concentrations 1
- Complete elimination: The active drug and glucuronide conjugate are fully eliminated from blood within 1 week following the last dose 3
Special Population Considerations
Age-related variations significantly affect lorazepam half-life in certain populations, though elderly adults show minimal changes. 4, 1
- Infants: Markedly prolonged half-life of approximately 40 hours 4
- Children: Half-life of approximately 10.5 hours 4
- Elderly adults: Mean total body clearance may decrease by approximately 20% compared to younger adults, though advancing age does not significantly affect overall pharmacokinetics 1
- Renal failure: May increase elimination half-life 4
- Hepatic dysfunction: Reduces benzodiazepine clearance 4
Clinical Implications for Dosing
The 12-hour half-life positions lorazepam in the intermediate-acting benzodiazepine category, with important clinical consequences. 5, 6
- Steady-state achievement: Occurs within 2-3 days of multiple-dose regimens, with blood levels directly proportional to daily dose 3
- Dosing frequency: The 12-hour half-life allows for twice-daily or three-times-daily dosing for continuous therapeutic effect 6
- Monitoring duration: For procedural sedation, patients require monitoring for up to 2 hours post-administration of IV lorazepam 4
- Preferred use in cirrhosis: Short half-life benzodiazepines like lorazepam are typically recommended in cirrhotic patients to avoid drug accumulation and encephalopathy risk, though controlled trials have not validated this preference 5
Comparison to Other Benzodiazepines
Lorazepam has a sixfold longer half-life than midazolam, which is clinically significant when converting between these agents, particularly in pediatric populations. 4