Le. Mather et al., BUPIVACAINE ENANTIOMER PHARMACOKINETICS AFTER INTERCOSTAL NEURAL BLOCKADE IN LIVER-TRANSPLANTATION PATIENTS, Anesthesia and analgesia, 80(2), 1995, pp. 328-335
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.