ATP-binding cassette transporter polymorphisms and the pharmacokinetics of oral esketamine
Jérôme C Oude Nijhuis, Daniël T Coerts, Jens H van Dalfsen, Sanne Y Smith-Apeldoorn, Jolien K E Veraart, Robert A Schoevers, Daan J Touw, Ron H N Van Schaik, Wim J. Tamminga
Pharmacogenomics December 12, 2025 DOI: 10.1080/14622416.2026.2617376 (opens in new tab)
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Study at a glance
AI-extracted from the abstract| Characteristics | Randomized controlled trial Placebo-controlled Peer reviewed |
|---|---|
| Sample size | 18 |
| Population | Adults with treatment-resistant depression |
| Intervention | oral esketamine |
| Dose | low dose |
| Topics | Ketamine Esketamine |
| Keywords | Pharmacokinetics Pharmacogenetics Genotype Genotyping Active metabolite Atp-binding cassette transporter Polymorphism computer science Clinical pharmacology Oral administration Cyp3a5 |
| Key findings | ABCB1 and ABCG2 transporter polymorphisms were not significantly associated with plasma concentrations of esketamine or its metabolites four hours after oral dosing. |
Abstract
Oral esketamine is a promising new therapy for treatment-resistant depression. However, concerns exist about interindividual pharmacokinetic variability. Genetic polymorphisms regulating the expression of ATP-binding cassette (ABC) transporters might influence bioavailability. Utilizing blood samples from a placebo-controlled trial investigating repeated, low dose oral esketamine (N = 18), we performed ABCB1 3435C > T and ABCG2 421C > A genotyping and measured the plasma levels of esketamine and its metabolites 4 h after dosing. For ABCB1 3435C > T, esketamine concentrations for C/C (Mdn = 3.8 µg/L), C/T (Mdn = 2.7 µg/L), and T/T (Mdn = 1.0 µg/L) were not significantly different (χ2(2) = 3.41, p = 0.182). For ABCG2 421C > A, esketamine concentrations did not differ significantly between C/A (Mdn = 1.5 µg/L) and C/C (Mdn = 2.4 µg/L) (U = 10.00, p = 0.471). Metabolite plasma concentrations were also not associated with polymorphism status. These results suggest that oral esketamine pharmacokinetics are unaffected by ABC transporter polymorphisms. However, due to the limited sample size and genotype variant representation, results are preliminary. Larger, more adequately powered studies are needed to clarify genotype effects and inform individualized esketamine therapyClinical trial registration: NTR6161 (Dutch Trial Register).
Comparable studies
Other randomized controlled trials on esketamine, most cited first.
Citations in the library
Cites 7
- Mechanisms of Ketamine and its Metabolites as Antidepressants Biochemical Pharmacology December 1, 2021
- Efficacy of single and repeated administration of ketamine in unipolar and bipolar depression: a meta-analysis of randomized clinical trials Pharmacological Reports April 16, 2020
- Long-Term Safety and Maintenance of Response With Esketamine Nasal Spray in Participants With Treatment-Resistant Depression: Interim Results of the SUSTAIN-3 Study Neuropsychopharmacology May 12, 2023
- Interaction of drugs of abuse and maintenance treatments with human P-glycoprotein (ABCB1) and breast cancer resistance protein (ABCG2). The International Journal of Neuropsychopharmacology August 1, 2010
- Oral ketamine for the treatment of pain and treatment-resistant depression The British Journal of Psychiatry February 1, 2016
and 2 more in the library