PHARMACOKINETICS OF BUPIVACAINE ENANTIOMERS DURING INTERPLEURAL INFUSION

Interpleural infusions (24 hr) were given to 14 adults (29-81 yr) havi ng surgery via right subcostal incisions. Patient-controlled analgesia with morphine was also available for 72 hours following surgery. An i nfusion of 0.25% bupivacaine with adrenaline 1/400,000 was commenced a t 0.1 ml/kg/hr at the conclusion of surgery after an initial 20 ml bol us. The 24 hr cumulative morphine dose increased by 62% (P<0.01) on th e second postoperative day after the bupivacaine infusion was ceased, but the pain score did not change. There was no clinical evidence of b upivacaine toxicity although the maximum bupivacaine concentration ran ged from 0.74-6.52 mg/l, mean 2.90 (SEM 0.44) mg/l and vascular uptake was rapid in two patients. The concentration of S-bupivacaine was con sistently greater than R-bupivacaine (P<0.05) and total body clearance was less. The unbound bupivacaine fraction also changed from 3.6% (SE M 0.6) at the start of the infusion to 2.0% (SEM 0.3) at 24 hr (P<0.00 5). The total body clearance of each enantiomer was reduced during the 24 hours (P<0.001). No relationship between pharmacokinetic parameter s and weight, age or sex was found (P>0.25 for each). Variation betwee n patients was reduced when parameters were estimated for the free (un bound) bupivacaine (P<0.001).