Stereoselective pharmacokinetics of ketamine: R(-)-ketamine inhibits the elimination of S(+)-ketamine.
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.
Ihmsen
H
H
Department of Anesthesiology, Friedrich-Alexander-University of Erlangen-Nuremberg, Erlangen, Germany. harald.ihmsen@kfa.imed.uni-erlangen.de
Geisslinger
G
G
Schüttler
J
J
D000328:Adult; D000778:Anesthetics, Dissociative / Q000493:pharmacokinetics*; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D007649:Ketamine / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000494:pharmacology; D008297:Male; D012119:Respiration / Q000187:drug effects; D013237:Stereoisomerism
D000778:Anesthetics, Dissociative; D007649:Ketamine