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  • Title: Stereoselective pharmacokinetics of ketamine: R(-)-ketamine inhibits the elimination of S(+)-ketamine.
    Author: Ihmsen H, Geisslinger G, Schüttler J.
    Journal: Clin Pharmacol Ther; 2001 Nov; 70(5):431-8. PubMed ID: 11719729.
    Abstract:
    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.
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