Lorazepam and oxazepam kinetics in women on low-dose oral contraceptives

Darrell R. Abernethy, David J. Greenblatt, Hermann R. Ochs, Dagmar Weyers, Marcia Divoll, Jerold S. Harmatz, Richard I. Shader

Research output: Contribution to journalArticlepeer-review

Abstract

Women on low-dose estrogen oral contraceptives (OC) and drug free control women matched for age, weight, and cigarette smoking habits, received single 2-mg 1V doses of lorazepam or single 30-mg oral doses of oxazepam, two benzodiazepines metabolized by glucuronide conjugation. Kinetics were determined.from multiple plasma concentrations measured during 48 hr after dosing. Mean kinetic variables for lorazepam in control and OC groups (n = 15 in each group) were: volume of distribution (Vd), 1.33 and 1.45 l/kg; elimination t 1 2, 13.1 and 12.2 hr; total clearance, 1.25 and 1.50 ml/min/kg; free fraction in plasma, 10.3% and 10.3% unbound. For oxazepam, kinetic variables in the two groups (n = 14 and 17) were: Vd, 1.05 and 1.19 l/kg; t 1 2 7.6 and 7.2 hr; total clearance, 1.60 and 2.03 ml/min/kg; free fraction, 4.6% and 4.9% unbound. None of these differences were significant. Thus, metabolic clearance by glucuronidation of lorazepam and oxazepam is not significantly affected by OC, in contrast with the highly significant reduction in clearance of the oxidized benzodiazepine diazepam.

Original languageEnglish (US)
Pages (from-to)628-632
Number of pages5
JournalClinical pharmacology and therapeutics
Volume33
Issue number5
DOIs
StatePublished - May 1983
Externally publishedYes

ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)

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