PHARMACOKINETICS OF LIDOCAINE AND ITS MAJOR METABOLITE - MONOETHYLGLYCINEXYLIDIDE (MEGX) IN RABBITS WITH EXPERIMENTAL COMMON BILE-DUCT OBSTRUCTION

The aim of this study was to evaluate, using an experimental model, th e effect of obstructive cholestasis on the pharmacokinetics of lidocai ne and the formation rate of its major metabolite - monoethylglycinexy lidide (MEGX) - in rabbits. The investigation was carried out on 20 ra bbits, randomly divided into two groups: a control one sham-operated a nd an experimental one - animals with biliary duct ligation. The measu rements, i,e, laboratory and pharmacodynamic tests, as well as pharmac okinetic 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, liv ers were examined macro- and microscopically and biochemical analysis of the liver microsomes was performed. Lidocaine was given intravenous ly, as a bolus of 6 mg/kg. Blood for pharmacokinetic assays was sample d within 6 h following the drug administration, and MEGX concentration was evaluated 15 min after lidocaine had been administered. The immun ofluorescence polarization method was employed for determination of li docaine and MEGX concentrations. The one-compartment open model was us ed for calculations. It was found that obstructive cholestasis in rabb its leads to slower lidocaine elimination from the body as well as to impaired formation of MEGX.