Exposure to Oral S-ketamine Is Unaffected by Itraconazole but Greatly Increased by Ticlopidine
| Autor: | Miia Turpeinen, Marko A. Peltoniemi, Pertti J. Neuvonen, Petri Reponen, Nora Hagelberg, Klaus T. Olkkola, Teijo I. Saari, Kari Laine |
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| Rok vydání: | 2011 |
| Předmět: |
Adult
Male Antifungal Agents Ticlopidine CYP3A Itraconazole Administration Oral Pharmacology Placebo law.invention Young Adult Double-Blind Method law medicine Cytochrome P-450 CYP3A Humans Drug Interactions Pharmacology (medical) Ketamine Anesthetics Dissociative Cross-Over Studies Clinical pharmacology business.industry Oxidoreductases N-Demethylating Crossover study Cytochrome P-450 CYP2B6 Area Under Curve Cytochrome P-450 CYP3A Inhibitors Female Aryl Hydrocarbon Hydroxylases business Platelet Aggregation Inhibitors medicine.drug S-ketamine |
| Zdroj: | Clinical Pharmacology & Therapeutics. 90:296-302 |
| ISSN: | 1532-6535 0009-9236 |
| DOI: | 10.1038/clpt.2011.140 |
| Popis: | 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 (AUC0–∞) 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 AUC0–∞ to ketamine AUC0–∞ 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 |
| Databáze: | OpenAIRE |
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