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Lorazepam fast-dissolving drug formulation (FDDF) and intravenous administrations as anaesthetic premedicants: A pharmacokinetic analysis

par Camu, Frédéric ;Maes, Viviane ;Van de Velde, Ann;Sevens, Claude
Référence European journal of anaesthesiology, 5, 4, page (261-268)
Publication Publié, 1988

Article révisé par les pairs

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Résumé :

The pharmacokinetics of lorazepam premedication were studied in 16 patients using two different formulations (intravenous and FDDF oral administrations). Arterial blood samples were taken at intervals for up to 600 min after administration of 4 mg of each formulation, and plasma lorazepam concentrations were determined by gas-chromatography with electron capture detection. Concentration-time data for individual subjects were analysed by model-independent methods. The derived pharmacokinetic parameters indicated a rapid distribution (median T( 1/2 ) λ1 i.v. = 15.2 min, median T( 1/2 ) λ1 oral = 31.6 min) into a steady-state volume of distribution approximating total body water, with long elimination half-life and a low clearance. V(dss) and clearance were similar with both treatments. The absorption of FDDF lorazepam was rapid in half of the patients and provided a high plasma concentration of lorazepam (C(max) = 61.8 ng ml-1) in a short time interval (T(max) = 58 min), but there were considerable inter-individual differences. This variability in absorption might explain why premedication with FDDF lorazepam is sometimes less effective than expected.