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Lorazepam and oxazepam kinetics in women on low‐dose oral contraceptives
Author(s) -
Abernethy Darrell R,
Greenblatt David J,
Ochs Hermann R,
Weyers Dagmar,
Divoli Marcia,
Harmatz Jerold S,
Shader Richard I
Publication year - 1983
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1038/clpt.1983.85
Subject(s) - oxazepam , glucuronidation , lorazepam , chemistry , free fraction , benzodiazepine , pharmacokinetics , volume of distribution , pharmacology , oral administration , glucuronide , dosing , medicine , anesthesia , metabolism , biochemistry , microsome , enzyme , receptor
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 IV 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 t½, 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: t½, 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. Clinical Pharmacology and Therapeutics (1983) 33, 628–632; doi: 10.1038/clpt.1983.85