Steady-state Pharmacokinetics of Interpleural Bupivacaine in Patients After Cholecystectomy

Venous plasma concentrations of bupivacaine were determined in eight cholecystectomy patients following multiple interpleural bolus instillations of bupivacaine 20 ml 0.5% with adrenaline (5 mg/l) administered at six- to eight-hour intervals. The mean steady-state peak plasma concentration was 2.3 mg/l (range 1.2-3.1 mg/l); however, in three of the eight patients peak plasma concentrations were greater than 3 mg/l. The mean accumulation ratio was found to be 1.6 (range 0.99-2.49), with steady-state occurring within the first 24 hours of drug administration. Mean apparent systemic plasma clearance was 0.16 +/- 0.07 l/kg/h with a mean terminal half-life of 5.8 +/- 2.3 hours measured at steady-state, values which were not significantly different (P greater than 0.05) from those values obtained following single interpleural bolus dose administration.