PHARMACOKINETICS OF THE ENANTIOMERS OF MEPIVACAINE AFTER INTRAVENOUS ADMINISTRATION OF THE RACEMATE IN VOLUNTEERS

The pharmacokinetics of R(-)-mepivacaine and S(+)-mepivacaine were inv estigated in 10 healthy volunteers. The volunteers received racemic me pivacaine, hydrochloride (dose 60 mg) via a 10-min intravenous infusio n. Blood samples were collected at gradually increasing intervals unti l 8 h after the start of the infusion. Plasma concentrations of the en antiomers were determined with a stereoselective high-performance liqu id chromatographic (HPLC) method. Unbound fractions of the enantiomers were determined using equilibrium dialysis. The unbound fraction of R (-)-mepivacaine (mean +/- SD: 35.6% +/- 4.5%) was larger (P < 0.0001) than that of S(+)-mepivacaine (25.1% +/- 4.6%). The total plasma clear ance and steady-state volume of distribution of R(-)-mepivacaine, base d on total plasma concentrations (total plasma clearance [CL] = 0.79 /- 0.12 L/min; volume of distribution at steady state [V-ss] = 103 +/- 14 L) as well as on unbound plasma concentrations (plasma clearance o f unbound drug [CL(u)] = 2.24 +/- 0.30 L/min; volume of distribution o f unbound drug at steady state [V-uss] = 290 +/- 32 L), were larger (P < 0.0001) than those of S(+)-mepivacaine (CL = 0.35 +/- 0.06 L/min; V -ss = 57 +/- 7 L; CL(u) = 1.43 +/- 0.24 L/min; V-uss = 232 +/- 30 L). The terminal half-life (t(1/2,Z)) and mean residence time (MRT) of R(- )-mepivacaine (t(1/2,Z) = 113 +/- 17 min; MRT = 131 +/- 15 min) were s horter than those of S(+)-mepivacaine (t(1/2,Z) = 123 +/- 20 min, P < 0.02; MRT = 165 +/- 24 min, P < 0.0001). This study demonstrated a mar ked difference in the pharmacokinetics of the enantiomers of mepivacai ne. The stereoselectivity can be partially explained by a difference i n the plasma protein binding of the enantiomers.