Journal
CLINICAL PHARMACOLOGY & THERAPEUTICS
Volume 70, Issue 5, Pages 431-438Publisher
MOSBY, INC
DOI: 10.1067/mcp.2001.119722
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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 mug (.) ml(-1) (.) min(-1) for S(+)-ketamine and 0.2 mug (.) ml(-1) (.) 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 (.) 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(+)-ketamine 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 elimination of S(+)-ketamine.
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