A1 Vertaisarvioitu alkuperäisartikkeli tieteellisessä lehdessä
St John's wort greatly decreases the plasma concentrations of oral S-ketamine
Tekijät: Peltoniemi MA, Saari TI, Hagelberg NM, Laine K, Neuvonen PJ, Olkkola KT
Kustantaja: WILEY-BLACKWELL
Julkaisuvuosi: 2012
Journal: Fundamental and Clinical Pharmacology
Tietokannassa oleva lehden nimi: FUNDAMENTAL & CLINICAL PHARMACOLOGY
Lehden akronyymi: FUND CLIN PHARMACOL
Numero sarjassa: 6
Vuosikerta: 26
Numero: 6
Aloitussivu: 743
Lopetussivu: 750
Sivujen määrä: 8
ISSN: 0767-3981
DOI: https://doi.org/10.1111/j.1472-8206.2011.00954.x
Tiivistelmä
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 Johns 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 Johns 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 Johns wort decreased the mean area under the plasma concentrationtime curve (AUC08) of ketamine by 58% (P < 0.001) and decreased the peak plasma concentration (Cmax) of ketamine by 66% (P < 0.001) when compared with placebo. Mean Cmax of norketamine (the major metabolite of ketamine) was decreased by 23% (P = 0.002) and mean AUC08 of norketamine by 18% (P < 0.001) by St Johns wort. There was a statistically significant linear correlation between the self-reported drug effect and Cmax of ketamine (r = 0.55; P < 0.01). St Johns 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 Johns wort.
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 Johns 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 Johns 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 Johns wort decreased the mean area under the plasma concentrationtime curve (AUC08) of ketamine by 58% (P < 0.001) and decreased the peak plasma concentration (Cmax) of ketamine by 66% (P < 0.001) when compared with placebo. Mean Cmax of norketamine (the major metabolite of ketamine) was decreased by 23% (P = 0.002) and mean AUC08 of norketamine by 18% (P < 0.001) by St Johns wort. There was a statistically significant linear correlation between the self-reported drug effect and Cmax of ketamine (r = 0.55; P < 0.01). St Johns 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 Johns wort.
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