PHARMACOKINETICS OF THE ENANTIOMERS OF BUPIVACAINE AND MEPIVACAINE AFTER EPIDURAL ADMINISTRATION OF THE RACEMATES

We investigated the pharmacokinetics of the enantiomers of bupivacaine and mepivacaine after epidural injection of the racemate of each drug into six surgical patients. After epidural administration of either b upivacaine/HCl (115 mg) or mepivacaine/HCl (460 mg), blood samples wer e collected for 24 h. Unbound fractions were determined by using ultra filtration for bupivacaine and equilibrium dialysis for mepivacaine. C oncentrations in plasma, ultrafiltrate, and dialysate were determined by using stereoselective high-performance liquid chromatography. Peak plasma concentrations of R(+)-bupivacaine (389 +/- 93 ng/mL) and R(-)- mepivacaine (1350 +/- 430 ng/mL) were smaller than those of S(-)-bupiv acaine (449 +/- 109 ng/mL, P < 0.0001) and S(+)-mepivacaine (1740 +/- 490 ng/mL, P < 0.002), respectively. However, the unbound peak concent rations of R(+)-bupivacaine (20 +/- 11 ng/mL) were larger than those o f S(-)-bupivacaine (15 +/- 9 ng/mL, P < 0.005); unbound peak concentra tions of R(-)-mepivacaine (485 +/- 158 ng/mL) and S(+)-mepivacaine (46 0 +/- 139 ng/mL) did not differ. These observations reflect difference s in the systemic disposition (distribution and elimination) of the en antiomers, because the systemic absorption was not enantioselective wi th either drug. This study supports the opinion that the use of single enantiomers, rather than racemates, is preferable, particularly for b upivacaine. Implications: Measurements of the plasma concentrations of the enantiomers of bupivacaine and mepivacaine after epidural adminis tration of the racemates demonstrated that the systemic disposition, b ut not the systemic absorption, of these drugs is enantioselective and supports the opinion that the use of single enantiomers, rather than racemates, is preferable.