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  • Title: Lorazepam and oxazepam kinetics in women on low-dose oral contraceptives.
    Author: Abernethy DR, Greenblatt DJ, Ochs HR, Weyers D, Divoll M, Harmatz JS, Shader RI.
    Journal: Clin Pharmacol Ther; 1983 May; 33(5):628-32. PubMed ID: 6132698.
    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 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 t1/2, 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; t1/2, 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. Women taking low-dose estrogen oral contraceptives (OCs) and drug-free control women matched for age, weight, and cigarette smoking habits, received single 2-mg intravenous doses of lorazepam or single 30-mg oral doses of oxazepam, 2 benzodiazepines metabolized by glucuronide conjugation. Kinetics were determined from multiple plasma concentrations measured during the 48 hours 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 1/kg; elimination t1/2, 13.1 and 12.2 hours; total clearance, 1.25 and 1.50 ml/minute/kg; free fraction in plasma, 10.3% and 10.3% unbound. For oxazepam, kinetic variables in the 2 groups (n=14 and 17) were: Vd, 1.05 and 1.19 1/kg; t1/2, 7.6 and 7.2 hours; total clearance, 1.60 and 2.03 ml/minute/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 OCs, in contrast with the highly significant reduction in clearance of the oxidized benzodiazepine diazepam.
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