A1 Vertaisarvioitu alkuperäisartikkeli tieteellisessä lehdessä
Exposure to Oral S-ketamine Is Unaffected by Itraconazole but Greatly Increased by Ticlopidine
Tekijät: Peltoniemi MA, Saari TI, Hagelberg NM, Reponen P, Turpeinen M, Laine K, Neuvonen PJ, Olkkola KT
Kustantaja: NATURE PUBLISHING GROUP
Julkaisuvuosi: 2011
Journal: Clinical Pharmacology and Therapeutics
Tietokannassa oleva lehden nimi: CLINICAL PHARMACOLOGY & THERAPEUTICS
Lehden akronyymi: CLIN PHARMACOL THER
Numero sarjassa: 2
Vuosikerta: 90
Numero: 2
Aloitussivu: 296
Lopetussivu: 302
Sivujen määrä: 7
ISSN: 0009-9236
DOI: https://doi.org/10.1038/clpt.2011.140
Tiivistelmä
This study examined drug-drug interactions of oral S-ketamine with the cytochrome P450 (CYP) 2B6 inhibitor ticlopidine and the CYP3A inhibitor itraconazole. In this randomized, blinded, crossover study, 11 healthy volunteers ingested 0.2 mg/kg S-ketamine after pretreatments with oral ticlopidine (250 mg twice daily), itraconazole (200 mg once daily), or placebo in 6-day treatment periods at intervals of 4 weeks. Ticlopidine treatment increased the mean area under the plasma concentration-time curve extrapolated to infinity (AUC(0-infinity)) of oral ketamine by 2.4-fold (P < 0.001), whereas itraconazole treatment did not increase the exposure to S-ketamine. The ratio of norketamine AUC(0-infinity) to ketamine AUC(0-infinity) was significantly decreased in the ticlopidine (P < 0.001) and itraconazole phases (P = 0.006) as compared to placebo. In the ticlopidine and itraconazole phases, the areas under the effect-time curves (self-reported drowsiness and performance) were significantly higher than those in the placebo phase (P < 0.05). The findings suggest that the dosage of S-ketamine should be reduced in patients receiving ticlopidine.
This study examined drug-drug interactions of oral S-ketamine with the cytochrome P450 (CYP) 2B6 inhibitor ticlopidine and the CYP3A inhibitor itraconazole. In this randomized, blinded, crossover study, 11 healthy volunteers ingested 0.2 mg/kg S-ketamine after pretreatments with oral ticlopidine (250 mg twice daily), itraconazole (200 mg once daily), or placebo in 6-day treatment periods at intervals of 4 weeks. Ticlopidine treatment increased the mean area under the plasma concentration-time curve extrapolated to infinity (AUC(0-infinity)) of oral ketamine by 2.4-fold (P < 0.001), whereas itraconazole treatment did not increase the exposure to S-ketamine. The ratio of norketamine AUC(0-infinity) to ketamine AUC(0-infinity) was significantly decreased in the ticlopidine (P < 0.001) and itraconazole phases (P = 0.006) as compared to placebo. In the ticlopidine and itraconazole phases, the areas under the effect-time curves (self-reported drowsiness and performance) were significantly higher than those in the placebo phase (P < 0.05). The findings suggest that the dosage of S-ketamine should be reduced in patients receiving ticlopidine.
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