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 0.2mg/kg S-ketamine after pretreatments with oral ticlopidine (250mg twice daily), itraconazole (200mg 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-) 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-to ketamine AUC 0-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. © 2011 american society for Clinical Pharmacology and therapeutics.
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