Objective: We investigated the pharmacokinetics of ketamine with special re
gard 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 rand
omized double-blind crossover study. Drugs were administered by a computer-
controlled device. Two infusion cycles with linearly increasing targets [sl
ope, 0.1 mug (.) ml(-1) (.) min(-1) for S(+)-ketamine and 0.2 mug (.) ml(-1
) (.) min(-1) for racemic ketamine] were administered. Concentrations of th
e ketamine enantiomers were determined from arterial blood, and pharmacokin
etic 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 (.) kg(-1) (.) min(-1)) compared with racemic ketamine (14.8 +/- 1.7
ml (.) kg(-1) (.) min(-1); P < .05) and R(-)-ketamine (13.8 +/- 1.3 ml (.)
kg(-1) (.) min(-1); P < .05). Furthermore, the clearance of the S(+)-ketami
ne was smaller in the racemate (18.5 +/- 0.7 ml (.) kg(-1) (.) min(-1); P <
.05) than for the pure isomer.
Conclusions: These results demonstrate that R(-)-ketamine inhibits the elim
ination of S(+)-ketamine.