Exposure to oral S-ketamine is unaffected by itraconazole but greatly increased by ticlopidine.

Author(s): Peltoniemi MA, Saari TI, Hagelberg NM, Reponen P, Turpeinen M, Laine K, Neuvonen PJ, Olkkola KT

Affiliation(s): Department of Anesthesiology, Intensive Care, Emergency Care and Pain Medicine, University of Turku and Turku University Hospital, Turku, Finland.

Publication date & source: 2011-08, Clin Pharmacol Ther., 90(2):296-302. Epub 2011 Jun 29.

Publication type: Randomized Controlled Trial; Research Support, Non-U.S. Gov't

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.