Influence of long-term infusions on lidocaine kinetics

Abstract

Lidocaine kinetics were examined during continuous infusions in 5 healthy subjects using stable isotope lidocaine labeled with 2 deuterium atoms. During phase 1, lidocaine and stable isotope lidocaine (50 mg i.v. each) were given as a bolus to confirm that the 2 species were kinetically identical. Phase 2 consisted of a long-term (30 h) lidocaine infusion designed to produce a steady-state concentration equal to 1.5 .mu.g/ml. At 24 h into the infusion stable isotope lidocaine (50 mg) was given as an i.v. bolus and kinetic parameters were calculated. Phase 3 differed from phase 2 in that the target steady-state lidocaine concentration was 4 .mu.g/ml and the stable isotope lidocaine dose was reduced to 40 mg. A gas chromatograph-mass spectrometer was used to determine lidocaine and stable isotope lidocaine serum concentrations. Compared to phase 1, clearance decreased (P < 0.05) and half-life increased (P < 0.025) during phases 2 and 3. The volume of distribution at steady-state remained constant during all 3 phases. Lidocaine cumulated in serum during long-term infusions in all 5 subjects; repeated decreases in infusion rate was necessary to avoid exceeding desire target concentrations in phases 2 and 3.