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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)

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Study at a glance

AI-extracted from the abstract
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
Topics Esketamine Ketamine
Key points 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

Comparable studies

Other randomized controlled trials on ketamine, most cited first.

Study Year Design Participants
Subanesthetic Effects of the Noncompetitive NMDA Antagonist, Ketamine, in Humans Healthy human subjects recruited from the community 1994 Randomized controlled trial n = 19
Antidepressant Efficacy of Ketamine in Treatment-Resistant Major Depression: A Two-Site Randomized Controlled Trial Patients with treatment-resistant major depression experiencing a major depressive episode 2013 Randomized controlled trial n = 73
Remifentanil-induced Postoperative Hyperalgesia and Its Prevention with Small-dose Ketamine Patients undergoing major abdominal surgery 2005 Randomized controlled trial n = 75
Efficacy of Intravenous Ketamine for Treatment of Chronic Posttraumatic Stress Disorder Patients with chronic PTSD related to a range of trauma exposures 2014 Randomized controlled trial n = 41
Ketamine-Induced Deficits in Auditory and Visual Context-Dependent Processing in Healthy Volunteers Healthy volunteers 2000 Single-blind placebo-controlled study n = 20

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