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St John’s wort greatly decreases the plasma concentrations of oral S‐ketamine

Marko A. Peltoniemi, Teijo I. Saari, Nora M. Hagelberg, Kari Laine, Pertti J. Neuvonen, Klaus Tapio Olkkola

Fundamental and Clinical Pharmacology June 2, 2011 DOI: 10.1111/j.1472-8206.2011.00954.x (opens in new tab)

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Study at a glance

AI-extracted from the abstract
Characteristics Randomized cross-over study Peer reviewed
Sample size 12
Population Healthy volunteers
Interventions St John's wort S-ketamine
Dose 0.3 mg/kg of S-ketamine
Duration 14-day pretreatment; plasma concentrations measured for 24 h and pharmacodynamic variables for 12 h after S-ketamine
Topics Esketamine Ketamine
Citations 44
Key points St John's wort markedly reduced exposure to oral S-ketamine: mean AUC(0-infinity) fell 58% and mean Cmax fell 66% versus placebo, with smaller reductions in norketamine Cmax (23%) and AUC (18%). Self-reported drug effect correlated with ketamine Cmax (r = 0.55). The authors report no significant changes in analgesic or behavioural effects, but warn that usual S-ketamine doses may become ineffective with concomitant St John's wort.

Abstract

Ketamine is an intravenous anaesthetic and analgesic agent but it can also be used orally as an adjuvant in the treatment of chronic pain. This study investigated the effect of the herbal antidepressant St John's wort, an inducer of cytochrome P450 3A4 (CYP3A4), on the pharmacokinetics and pharmacodynamics of oral S-ketamine. In a randomized cross-over study with two phases, 12 healthy subjects were pretreated with oral St John's wort or placebo for 14 days. On day 14, they were given an oral dose of 0.3 mg/kg of S-ketamine. Plasma concentrations of ketamine and norketamine were measured for 24 h and pharmacodynamic variables for 12 h. St John's wort decreased the mean area under the plasma concentration-time curve (AUC(0-∞)) of ketamine by 58% (P < 0.001) and decreased the peak plasma concentration (C(max)) of ketamine by 66% (P < 0.001) when compared with placebo. Mean C(max) of norketamine (the major metabolite of ketamine) was decreased by 23% (P = 0.002) and mean AUC(0-∞) of norketamine by 18% (P < 0.001) by St John's wort. There was a statistically significant linear correlation between the self-reported drug effect and C(max) of ketamine (r = 0.55; P < 0.01). St John's wort greatly decreased the exposure to oral S-ketamine in healthy volunteers. Although this decrease was not associated with significant changes in the analgesic or behavioural effects of ketamine in the present study, usual doses of S-ketamine may become ineffective if used concomitantly with St John's wort.

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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Esketamine Ketamine