J. Wojcicki et al., PHARMACOKINETICS OF LIDOCAINE AND ITS MAJOR METABOLITE - MONOETHYLGLYCINEXYLIDIDE (MEGX) IN RABBITS WITH EXPERIMENTAL COMMON BILE-DUCT OBSTRUCTION, European journal of drug metabolism and pharmacokinetics, 20(2), 1995, pp. 119-123
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.