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St John's wort greatly decreases the plasma concentrations of oral S-ketamine.
- Source :
-
Fundamental & clinical pharmacology [Fundam Clin Pharmacol] 2012 Dec; Vol. 26 (6), pp. 743-50. Date of Electronic Publication: 2011 Jun 02. - Publication Year :
- 2012
-
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.<br /> (© 2011 The Authors Fundamental and Clinical Pharmacology © 2011 Société Française de Pharmacologie et de Thérapeutique.)
- Subjects :
- Adult
Analgesics administration & dosage
Analgesics adverse effects
Analgesics pharmacology
Antidepressive Agents administration & dosage
Antidepressive Agents adverse effects
Cross-Over Studies
Dose-Response Relationship, Drug
Drug Interactions
Female
Half-Life
Humans
Ketamine administration & dosage
Ketamine adverse effects
Ketamine blood
Ketamine pharmacology
Male
Neuropsychological Tests
Plant Preparations administration & dosage
Plant Preparations adverse effects
Psychomotor Performance drug effects
Regression Analysis
Young Adult
Analgesics blood
Antidepressive Agents pharmacology
Hypericum chemistry
Ketamine analogs & derivatives
Plant Preparations pharmacology
Subjects
Details
- Language :
- English
- ISSN :
- 1472-8206
- Volume :
- 26
- Issue :
- 6
- Database :
- MEDLINE
- Journal :
- Fundamental & clinical pharmacology
- Publication Type :
- Academic Journal
- Accession number :
- 21635359
- Full Text :
- https://doi.org/10.1111/j.1472-8206.2011.00954.x