Clinical pharmacokinetics of oxazepam and lorazepam

Clin Pharmacokinet. Mar-Apr 1981;6(2):89-105. doi: 10.2165/00003088-198106020-00001.

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%).

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.
  • Review

MeSH terms

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

Substances

  • Anti-Anxiety Agents
  • Oxazepam
  • Lorazepam