Abstract
The aim of this study was to evaluate, using an experimental model, the effect of obstructive cholestasis on the pharmacokinetics of lidocaine and the formation rate of its major metabolite- monoethylglycinexylidide (MEGX)-in rabbits. The investigation was carried out on 20 rabbits, randomly divided into two groups: a control one sham-operated and an experimental one-animals with biliary duct ligation. The measurements, i.e. laboratory and pharmacodynamic tests, as well as pharmacokinetic assays were performed prior to the operation as well as 10-12 days after the bile duct ligation. At the end stage of the study, livers were examined macro- and microscopically and biochemical analysis of the liver microsomes were performed. Lidocaine was given intravenously, as a bolus of 6 mg/kg. Blood for pharmacokinetic assay was sampled within 6 h following the drug administration, and MEGX concentration was evaluated 15 min after lidocaine had been administered. The immunofluorescence polarization method was employed for determination of lidocaine and MEGX concentrations. The one-compartment open model was used for calculations.
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