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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
Publication year - 2011
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1038/clpt.2011.140
Subject(s) - itraconazole , ticlopidine , crossover study , placebo , pharmacology , pharmacokinetics , ketamine , oral administration , area under the curve , medicine , ketoconazole , anesthesia , aspirin , pathology , antifungal , alternative medicine , dermatology , clopidogrel
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–∞ ) 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. Clinical Pharmacology & Therapeutics (2011) 90 2, 296–302. doi: 10.1038/clpt.2011.140