Pharmacokinetics of the enantiomers of bupivacaine and mepivacaine after epidural administration of the racemates

• Published in: Anesthesia and analgesia Vol. 86; no. 2; pp. 361 - 366
• Main Authors: GROEN, K, MANTEL, M, ZEIJLMANS, P. W. M, ZEPPENFELDT, B, OLIEMAN, W, STIENSTRA, R, VAN KLEEF, J. W, BURM, A. G. L
• Format: Conference Proceeding Journal Article
• Language: English
• Published: Hagerstown, MD Lippincott 01.02.1998
• Subjects: Adult; Anesthetics. Neuromuscular blocking agents; Area Under Curve; Biological and medical sciences; Bupivacaine - chemistry; Bupivacaine - pharmacokinetics; Humans; Injections, Epidural; Injections, Intravenous; Medical sciences; Mepivacaine - chemistry; Mepivacaine - pharmacokinetics; Middle Aged; Neuropharmacology; Pharmacology. Drug treatments; Stereoisomerism; Structure-Activity Relationship; Local anesthetic; Human; Bupivacaine; Mepivacaine; Enantiomer; Extradural administration; Racemate; Stereospecificity; Organic amide; Pharmacokinetics; Anilide
• ISSN: 0003-2999; 1526-7598
• DOI: 10.1097/00000539-199802000-00027

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 bupivacaine/HCl (115 mg) or mepivacaine/HCl (460 mg), blood samples were collected for 24 h. Unbound fractions were determined by using ultrafiltration for bupivacaine and equilibrium dialysis for mepivacaine. Concentrations 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(-)-bupivacaine (449 +/- 109 ng/mL, P < 0.0001) and S(+)-mepivacaine (1740 +/- 490 ng/mL, P < 0.002), respectively. However, the unbound peak concentrations of R(+)-bupivacaine (20 +/- 11 ng/mL) were larger than those of S(-)-bupivacaine (15 +/- 9 ng/mL, P < 0.005); unbound peak concentrations of R(-)-mepivacaine (485 +/- 158 ng/mL) and S(+)-mepivacaine (460 +/- 139 ng/mL) did not differ. These observations reflect differences in the systemic disposition (distribution and elimination) of the enantiomers, because the systemic absorption was not enantioselective with either drug. This study supports the opinion that the use of single enantiomers, rather than racemates, is preferable, particularly for bupivacaine. Measurements of the plasma concentrations of the enantiomers of bupivacaine and mepivacaine after epidural administration of the racemates demonstrated that the systemic disposition, but not the systemic absorption, of these drugs is enantioselective and supports the opinion that the use of single enantiomers, rather than racemates, is preferable.