Pharmacokinetics of prilocaine after intravenous administration in volunteers - Enantioselectivity

Background: Prilocaine exists in two stereoisomeric configurations, the ena ntiomers S(+)- and R(-)-prilocaine. The drug is clinically used as the race mate. This study examined the pharmacokinetics of the enantiomers after int ravenous administration of the racemate. Methods: Ten healthy male volunteers received 200 mg racemic prilocaine as a 10-min intravenous infusion. Blood samples were collected for 8 h after t he start of the infusion. Plasma concentrations were measured by stereosele ctive high-performance liquid chromatography (HPLC), Unbound fractions of t he enantiomers in blank blood samples, spiked with racemic prilocaine, were determined using equilibrium dial I sis. Results: The unbound fraction of R(-)-prilocaine (mean +/- SD, 70% +/- 8%), , smaller (P < 0.05) than that of S(+)-prilocaine (73% +/- 5%). The total p lasma clearance of R(-)-prilocaine (2.57 +/- 0.46 l/min) was larger (P < 0. 0001) than that of S(+)-prilocaine (1.91 +/- 0.30 l/min), The steady-state volume of distribution of R(-)-prilocaine (279 +/- 94 l) did not differ fro m that of S(+)-prilocaine (291 +/- 93 l), The terminal half-life of R(-)pri locaine (87 +/- 27 min) was shorter (P < 0.05) than that of S(+)-prilocaine (124 +/- 64 min), as was the mean residence time of R(-)-prilocaine (108 /- 30 min) compared with S(+)-prilocaine (155 +/- 59 min; P < 0.005), Conclusions: The pharmacokinetics of prilocaine are enantioselective. The d ifference in clearance is most likely a result of a difference In intrinsic metabolic clearance. The difference in the pharmacokinetics of the enantio mers of prilocaine does not seem to be clinically relevant.