Stereoselective pharmacokinetics of ketamine: R(-)-ketamine inhibits the elimination of S(+)-ketamine

Clin Pharmacol Ther. 2001 Nov;70(5):431-8. doi: 10.1067/mcp.2001.119722.


Objective: We investigated the pharmacokinetics of ketamine with special regard to enantiomer-specific differences.

Methods: Ten healthy young male volunteers (mean age, 28 +/- 4 years; mean weight, 79 +/- 11 kg) received racemic ketamine and S(+)-ketamine in a randomized double-blind crossover study. Drugs were administered by a computer-controlled device. Two infusion cycles with linearly increasing targets [slope, 0.1 microg x ml(-1) x min(-1) for S(+)-ketamine and 0.2 microg x ml(-1) x min(-1) for racemic ketamine] were administered. Concentrations of the ketamine enantiomers were determined from arterial blood, and pharmacokinetic parameters were estimated with a 2- and 3-compartment model.

Results: The total doses needed to reach defined end points were 271 +/- 80 mg and 409 +/- 75 mg for S(+)-ketamine and racemic ketamine, respectively (P <.05). S(+)-ketamine showed a significantly higher clearance (26.3 +/- 3.5 ml x kg(-1) x min(-1)) compared with racemic ketamine (14.8 +/- 1.7 ml x kg(-1) x min(-1); P <.05) and R(-)-ketamine (13.8 +/- 1.3 ml x kg(-1) x min(-1); P <.05). Furthermore, the clearance of the S (+)-ketamine was smaller in the racemate (18.5 +/- 0.7 ml x kg(-1) x min(-1); P <.05) than for the pure isomer.

Conclusions: These results demonstrate that R(-)-ketamine inhibits the elimination of S(+)-ketamine.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Anesthetics, Dissociative / pharmacokinetics*
  • Hemodynamics / drug effects
  • Humans
  • Ketamine / adverse effects
  • Ketamine / pharmacokinetics*
  • Ketamine / pharmacology
  • Male
  • Respiration / drug effects
  • Stereoisomerism


  • Anesthetics, Dissociative
  • Ketamine