title: Pharmacokinetics of prilocaine after intravenous administration in volunteers: enantioselectivity.
abstract: BACKGROUND
  Prilocaine exists in two stereoisomeric configurations, the enantiomers S(+)- and R(-)-prilocaine. The drug is clinically used as the racemate. This study examined the pharmacokinetics of the enantiomers after intravenous 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 the start of the infusion. Plasma concentrations were measured by stereoselective high-performance liquid chromatography (HPLC). Unbound fractions of the enantiomers in blank blood samples, spiked with racemic prilocaine, were determined using equilibrium dialysis.
  
  
  RESULTS
  The unbound fraction of R(-)-prilocaine (mean +/- SD, 70%+/-8%) was smaller (P < 0.05) than that of S(+)-prilocaine (73%+/-5%). The total plasma 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 from that of S(+)-prilocaine (291+/-93 l). The terminal half-life of R(-)-prilocaine (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 difference in clearance is most likely a result of a difference in intrinsic metabolic clearance. The difference in the pharmacokinetics of the enantiomers of prilocaine does not seem to be clinically relevant.
authors: Department of Anesthesiology, Leiden University Medical Center, The Netherlands. ameer@anst.azl.nl
authors: A D
authors: AD
authors: van der Meer
authors: A G
authors: AG
authors: Burm
authors: R
authors: R
authors: Stienstra
authors: J W
authors: JW
authors: van Kleef
authors: A A
authors: AA
authors: Vletter
authors: W
authors: W
authors: Olieman
mesh_terms: D000328:Adult; D000779:Anesthetics, Local / Q000493:pharmacokinetics*; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D011318:Prilocaine / Q000008:administration & dosage / Q000493:pharmacokinetics*; D013237:Stereoisomerism
chemical_list: D000779:Anesthetics, Local; D011318:Prilocaine