Clinical pharmacokinetics of oxazepam and lorazepam.

Abstract

Oxazepam and lorazepam are 3-hydroxy benzodiazepine derivatives used as sedatives and anxiolytics. The major metabolic pathway for both compounds involves conjugation to glucuronic acid at the 3-position, followed by urinary excretion of the inactive glucuronide metabolite. Oxazepam has been administered to humans by the oral route only. Usual ranges for kinetic parameters are: elimination half-life, 5 to 15 hours; volume of distribution, 0.6 to 2.0 L/kg; clearance, 0.9 to 2.0 ml/min/kg. Age and liver disease have a minimal influence on oxazepam kinetics, but renal disease is associated with a prolonged half-life and increased volume of distribution. Typical kinetic values for lorazepam are: elimination half-life, 8 to 25 hours; volume of distribution, 1.0 to 1.3 L/kg; clearance, 0.7 to 1.2 ml/min/kg. Lorazepam clearance is somewhat reduced in old age, but liver disease has a minimal effect on clearance. Oral and intramuscular lorazepam are rapidly absorbed, with systemic availability averaging 90% or more. Both oxazepam and lorazepam are extensively bound to plasma protein, but the free fraction for lorazepam (8 to 12%) is greater than that for oxazepam (2 to 4%).

• Authors: D J Greenblatt
• Journal: Clinical pharmacokinetics (Clin Pharmacokinet) 1981 Mar-Apr Vol. 6 Issue 2 Pg. 89-105 ISSN: 0312-5963 [Print] Switzerland
• PMID: 6111408 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S., Review)

Chemical References

• Anti-Anxiety Agents
• Oxazepam
• Lorazepam

Topics

• Aging
• Anti-Anxiety Agents (metabolism)
• Drug Interactions
• Female
• Humans
• Kidney Diseases (metabolism)
• Kinetics
• Liver Diseases (metabolism)
• Lorazepam (administration & dosage, metabolism)
• Oxazepam (administration & dosage, metabolism)
• Pregnancy