BUPIVACAINE ENANTIOMER PHARMACOKINETICS AFTER INTERCOSTAL NEURAL BLOCKADE IN LIVER-TRANSPLANTATION PATIENTS

Bupivacaine, being a racemic local anesthetic, exists as an equal mixt ure of its component enantiomers R(+)- and S(-)-bupivacaine, which beh ave pharmacokinetically as independent drugs after injection into the body. Intercostal neural blockade using bupivacaine was performed for postoperative analgesia in 12 patients after orthotopic Liver transpla ntation. Arterial blood, sampled serially, was assayed by enantioselec tive high-performance liquid chromatography for R(+)- and S(-)-bupivac aine. The average of the simultaneous R(+):S(-) ratios of blood bupiva caine concentrations in the 12 patients was 0.74 (SD 0.11); however, t he use of a population mean value or a mean value for any patient deni es the time-dependence of this entity. The blood enantiomer concentrat ion difference was reflected in the maximum measured concentrations wh ich, after the first dose, were, respectively, 0.38 (SD 0.19) and 0.52 (SD 0.28) mg.L(-1).100 mg(-1) RS-bupivacaine administered (P = 0.0003 ). The difference in blood concentrations between the enantiomers, ref lected by the R(+):S(-) ratio being less than unity, could be explaine d by a greater mean total body clearance and a larger apparent volume distribution of R(+)-bupivacaine. Elimination of both enantiomers was prolonged in these patients after liver transplantation compared to da ta from the literature, but there was no tendency for either enantiome r to accumulate selectively, even upon repeated dosing. We conclude th at this demonstration of differences in pharmacokinetics (and, in labo ratory studies, also in pharmacodynamics) between the bupivacaine enan tiomers points to the need for future studies to recognize the enantio meric duality of this local anesthetic.