Half life of lorazepam
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Half-Life of Lorazepam: A Comprehensive Overview
Introduction to Lorazepam Pharmacokinetics
Lorazepam, a 3-hydroxy, 1,4-benzodiazepine, is widely used for its sedative and anxiolytic properties. Understanding its pharmacokinetics, particularly its half-life, is crucial for optimizing therapeutic regimens and managing potential side effects.
Elimination Half-Life of Lorazepam
General Population
The elimination half-life of lorazepam varies significantly among individuals, typically ranging from 8 to 25 hours1. This variability can be attributed to differences in metabolic rates and individual patient characteristics.
Specific Studies and Findings
Several studies have provided more precise estimates of lorazepam's half-life. One study reported an average elimination half-life of about 12 hours following oral administration2. Another study, which involved intravenous administration, found a similar half-life of approximately 13.8 hours8. These findings are consistent across different administration routes, including oral, intramuscular, and intravenous10.
Factors Influencing Lorazepam Half-Life
Age and Clearance
Age appears to have a modest impact on lorazepam's pharmacokinetics. In elderly subjects, the elimination half-life was found to be around 15.9 hours, slightly longer than the 14.1 hours observed in younger individuals4. This difference is partly due to reduced clearance rates in older adults, which were 22% lower compared to younger subjects4.
Overdose Scenarios
In cases of lorazepam overdose, the elimination half-life remains consistent with that observed at therapeutic doses, indicating that the drug's pharmacokinetics do not change significantly even at higher concentrations3.
Enterohepatic Recirculation
Lorazepam undergoes significant enterohepatic recirculation, which can affect its half-life. Treatments that disrupt this process, such as the administration of neomycin and cholestyramine, have been shown to reduce the half-life by 19% to 26%9.
Conclusion
The elimination half-life of lorazepam generally ranges from 8 to 25 hours, with an average around 12 to 14 hours in most studies. Factors such as age, clearance rates, and enterohepatic recirculation can influence this parameter. Understanding these variations is essential for tailoring lorazepam therapy to individual patient needs and ensuring effective and safe use of the medication.
Sources and full results
Most relevant research papers on this topic
Clinical Pharmacokinetics of Oxazepam and Lorazepam
Oxazepam and lorazepam are both 3-hydroxy benzodiazepine derivatives used as sedatives and anxiolytics, with lorazepam showing a longer elimination half-life and faster clearance.
Highly CitedClinical pharmacokinetics of lorazepam: a review.
Lorazepam is rapidly absorbed, reaches peak blood levels within 2 hours, and is completely eliminated from the blood within 1 week after the last dose.
Highly CitedPharmacokinetic study of lorazepam overdosage.
Lorazepam overdosage can lead to clinical well-being within 24-30 hours, with high concentrations persisting, but the elimination half-life is similar to that of usual therapeutic doses.
Case ReportLorazepam kinetics in the elderly
Elderly individuals experience small changes in lorazepam kinetics, but both intramuscular and oral administration lead to rapid and nearly complete absorption into the systemic circulation.
Observational StudyHighly CitedClinical pharmacokinetics of lorazepam. I. Absorption and disposition of oral 14C-lorazepam.
Lorazepam is absorbed with a 15-minute half-life, peaking at 16.9 ng/ml, and its main clearance mechanism is biotransformation to a pharmacologically inactive glucuronide metabolite.
Non-RCTClorazepate and lorazepam: clinical improvement and rebound anxiety.
70% of anxious patients maintained improvement during a 2-week placebo period, but rebound anxiety was more intense and occurred earlier with lorazepam than with clorazepate.
RCTClinical pharmacokinetics of lorazepam; II. Intramuscular injection
Lorazepam is rapidly absorbed from intramuscular injections, reaching peak concentrations within 3 hours, and its major metabolite, lorazepam glucuronide, is rapidly produced and eliminated in parallel with the parent drug.
Non-RCTKinetics and dynamics of lorazepam during and after continuous intravenous infusion
Continuous infusion of lorazepam, preceded by a bolus loading dose, produces a relatively constant sedative effect on the central nervous system, suitable for critical care medicine.
Non-RCTDisposition of lorazepam in human beings: Enterohepatic recirculation and first‐pass effect
Lorazepam undergoes significant enterohepatic recirculation and has an extrahepatic pathway, making it unsuitable as a marker of conjugative metabolism.
Non-RCTPharmacokinetics and Bioavailability of Intravenous, Intramuscular, and Oral Lorazepam in Humans
Intravenous, intramuscular, and oral lorazepam all show dose-independent absorption kinetics, with oral lorazepam absorption being first order and intramuscular injection being first order.
Non-RCTHighly Cited