Stereoselective pharmacokinetics of ketamine: R(−)‐Ketamine inhibits the elimination of S(+)‐ketamine
Harald Ihmsen, Gerd Geisslinger, Jürgen Schüttler
Clinical Pharmacology & Therapeutics November 1, 2001 DOI: 10.1016/s0009-9236(01)06321-4 (opens in new tab)
Summary
AI-generated from the abstractIn a randomized double-blind crossover study, ten healthy young men received racemic ketamine and S(+)-ketamine via computer-controlled infusion. S(+)-ketamine required a lower total dose to reach defined endpoints (271 ± 80 mg) compared with racemic ketamine (409 ± 75 mg). S(+)-ketamine had significantly higher clearance (26.3 ± 3.5 ml·kg⁻¹·min⁻¹) than racemic ketamine (14.8 ± 1.7) and R(−)-ketamine (13.8 ± 1.3). Within the racemate, S(+)-ketamine clearance was lower (18.5 ± 0.7) than when given alone. The authors conclude that R(−)-ketamine inhibits the elimination of S(+)-ketamine.
Study at a glance
| Characteristics | Randomized double-blind crossover study Peer reviewed |
|---|---|
| Sample size | 10 |
| Population | Healthy young male volunteers |
| Intervention | Racemic ketamine |
| Dose | Infusion cycles with linearly increasing targets: slope 0.1 μg·ml⁻¹·min⁻¹ for S(+)-ketamine and 0.2 μg·ml⁻¹·min⁻¹ for racemic ketamine |
| Key finding | R(−)-ketamine inhibits the elimination of S(+)-ketamine, as evidenced by lower clearance of S(+)-ketamine when administered as racemic ketamine compared with the pure isomer. |
Abstract
ObjectiveWe investigated the pharmacokinetics of ketamine with special regard to enantiomer‐specific differences.MethodsTen 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 μg · ml−1 · min−1 for S(+)‐ketamine and 0.2 μg · 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.ResultsThe 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.ConclusionsThese results demonstrate that R(−)‐ketamine inhibits the elimination of S(+)‐ketamine.Clinical Pharmacology & Therapeutics (2001) 70, 431–438; doi: 10.1016/S0009‐9236(01)06321‐4