Clinical pharmacokinetics of R(+)- and S(-)-mepivacaine after high doses of racemic mepivacaine with epinephrine in the combined psoas compartment/sciatic nerve block.
The purpose of this study was to investigate the pharmacokinetics of R(+)- and S(-)-mepivacaine in 10 male patients after injection of a high dose (731 mg) of racemic R,S-mepivacaine for a combined psoas compartment/sciatic nerve block. Arterial blood samples were taken, and the plasma concentrations of the stereoisomers R(+)- and S(-)-mepivacaine were measured by means of high-performance liquid chromatography (HPLC) with a Chiral AGP column. The S(-) isomer reached higher plasma concentrations than the R(+) isomer. The maximal plasma concentration (Cmax) of R(+) was 1.54 +/- 0.34 micrograms/mL, whereas that of the S(-) isomer was 2.34 +/- 0.51 micrograms/mL (P = 0.00050). The time at which Cmax was reached (Tmax) was identical for both isomers. The area under the plasma concentration-time curve from t = 0 to infinity (AUC infinity) of S(-)-mepivacaine was almost double that of R(+)-mepivacaine. The elimination half-life (T1/2) was identical for both isomers (3 h), which means that the calculated total body clearance and the calculated steady-state volume of the distribution of R(+) are, respectively, 1.7 and 1.5 times larger than that of the S(-) isomer. We conclude that the plasma concentrations of the S(-)-mepivacaine isomer were higher than those of the R(+) isomer because of a smaller volume of distribution and a slower total body clearance.
Vree
T B
TB
Institute of Anesthesiology, Academic Hospital Nijmegen Sint Radboud, The Netherlands.
Beumer
E M
EM
Lagerwerf
A J
AJ
Simon
M A
MA
Gielen
M J
MJ
D000328:Adult; D000772:Anesthesia, Local; D002851:Chromatography, High Pressure Liquid; D004837:Epinephrine; D006801:Humans; D008297:Male; D008619:Mepivacaine / Q000097:blood / Q000493:pharmacokinetics*; D009132:Muscles / Q000294:innervation*; D009407:Nerve Block; D012584:Sciatic Nerve; D013237:Stereoisomerism
D008619:Mepivacaine; D004837:Epinephrine