Clinical pharmacokinetics of oxazepam and lorazepam.
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%).
D000375:Aging; D014151:Anti-Anxiety Agents / Q000378:metabolism*; D004347:Drug Interactions; D005260:Female; D006801:Humans; D007674:Kidney Diseases / Q000378:metabolism; D007700:Kinetics; D008107:Liver Diseases / Q000378:metabolism; D008140:Lorazepam / Q000008:administration & dosage / Q000378:metabolism*; D010076:Oxazepam / Q000008:administration & dosage / Q000378:metabolism*; D011247:Pregnancy
D014151:Anti-Anxiety Agents; D010076:Oxazepam; D008140:Lorazepam