Exposure to oral S-ketamine is unaffected by itraconazole but greatly increased by ticlopidine.
Marko A. Peltoniemi, Teijo I. Saari, Nora M. Hagelberg, P Reponen, M Turpeinen, Kari Laine, Pertti J. Neuvonen, K T Olkkola
Clinical Pharmacology & Therapeutics August 2011 DOI: 10.1038/clpt.2011.140 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Randomized, blinded, crossover study Peer reviewed |
|---|---|
| Sample size | 11 |
| Population | Healthy volunteers |
| Interventions | S-ketamine Ticlopidine Itraconazole |
| Dose | 0.2 mg/kg S-ketamine; ticlopidine 250 mg twice daily; itraconazole 200 mg once daily |
| Duration | 6-day treatment periods at intervals of 4 weeks |
| Measures | area under the plasma concentration-time curve extrapolated to infinity (AUC(0-∞)), ratio of norketamine AUC(0-∞) to ketamine AUC(0-∞), areas under the effect-time curves (self-reported drowsiness and performance) |
| Topics | Esketamine Ketamine |
| Key points | Ticlopidine increased the AUC(0-∞) of oral S-ketamine by 2.4-fold, whereas itraconazole did not increase exposure. Both pretreatments lowered the norketamine-to-ketamine ratio and increased self-reported drowsiness and performance effects, suggesting a need to reduce S-ketamine dose with ticlopidine. |
Abstract
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.
Comparable studies
Other randomized controlled trials on esketamine, most cited first.
Citations in the library
Cited by 5
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- The clinical toxicology of ketamine Clinical Toxicology June 2, 2023
- Ketamine metabolism via hepatic CYP450 isoforms contributes to its sustained antidepressant actions. Neuropharmacology November 1, 2024
- Metabolism and metabolomics of ketamine: a toxicological approach Forensic Sciences Research January 2, 2017
- (2R,6R)-Hydroxynorketamine is not essential for the antidepressant actions of (R)-ketamine in mice. Neuropsychopharmacology August 2018