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S-ketamine concentrations are greatly increased by grapefruit juice

  • Pharmacokinetics and Disposition
  • Published:
European Journal of Clinical Pharmacology Aims and scope Submit manuscript

Abstract

Purpose

We examined the effect of grapefruit juice on the pharmacokinetics and pharmacodynamics of oral S-ketamine.

Methods

A randomized crossover open-label study design with two phases at an interval of 4 weeks was conducted in 12 healthy volunteers. Grapefruit juice or water was ingested 200 ml t.i.d. for 5 days. An oral dose of 0.2 mg/kg of S-ketamine was ingested on day 5 with 150 ml grapefruit juice or water. Plasma concentrations of ketamine and norketamine were determined for 24 h, and pharmacodynamic variables were recorded for 12 h. Noncompartmental methods were used to calculate pharmacokinetic parameters.

Results

Grapefruit juice increased the geometric mean value of the area under the plasma ketamine concentration–time curve (AUC0–∞) by 3.0-fold (range 2.4- to 3.6-fold; P < 0.001), the peak plasma concentration (Cmax) by 2.1-fold (range 1.8- to 2.6-fold; P < 0.001), and the elimination half-life by 24% (P < 0.05) as compared to the water phase. The ratio of main metabolite norketamine to ketamine (AUCm/AUCp) was decreased by 57% (P < 0.001) during the grapefruit phase. Self-rated relaxation was decreased (P < 0.05) and the performance in the digit symbol substitution test was increased (P < 0.05) after grapefruit juice, but other behavioral or analgesic effects were not affected.

Conclusions

Grapefruit juice significantly increased the plasma concentrations of oral ketamine in healthy volunteers. Dose reductions of ketamine should be considered when using oral ketamine concomitantly with grapefruit juice.

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Acknowledgments

We want to thank Mrs. Elina Kahra (medical laboratory technologist, Clinical Pharmacology, TYKSLAB, Hospital District of Southwest Finland, Turku, Finland) for her skillful technical assistance.

Financial support

Turku University Hospital research fund EVO 13821, Turku, Finland; Instrumentarium Research Foundation, Helsinki, Finland and Sigrid Juselius Foundation, Helsinki, Finland

Conflict on interest

None.

Author information

Authors and Affiliations

  1. Department of Anesthesiology, Intensive Care, Emergency Care and Pain Medicine, University of Turku, P.O. Box 52, Kiinamyllynkatu 4-8, FI-20520, Turku, Finland

    Marko A. Peltoniemi, Nora M. Hagelberg & Klaus T. Olkkola

  2. Turku University Hospital, Turku, Finland

    Marko A. Peltoniemi, Nora M. Hagelberg & Klaus T. Olkkola

  3. Department of Anesthesiology, Friedrich-Alexander University Erlangen-Nuremberg, Erlangen, Germany

    Teijo I. Saari

  4. Department of Pharmacology, Drug Development and Therapeutics, University of Turku, Turku, Finland

    Kari Laine

  5. Unit of Clinical Pharmacology, Turku University Hospital, Turku, Finland

    Kari Laine

  6. Department of Clinical Pharmacology, University of Helsinki, Helsinki, Finland

    Pertti J. Neuvonen

  7. Helsinki University Central Hospital, Helsinki, Finland

    Pertti J. Neuvonen

Authors
  1. Marko A. Peltoniemi
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  2. Teijo I. Saari
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  3. Nora M. Hagelberg
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  4. Kari Laine
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  5. Pertti J. Neuvonen
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  6. Klaus T. Olkkola
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Corresponding author

Correspondence to Klaus T. Olkkola.

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Peltoniemi, M.A., Saari, T.I., Hagelberg, N.M. et al. S-ketamine concentrations are greatly increased by grapefruit juice. Eur J Clin Pharmacol 68, 979–986 (2012). https://doi.org/10.1007/s00228-012-1214-9

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  • DOI: https://doi.org/10.1007/s00228-012-1214-9

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