Pharmacokinetics and brain distribution of ketamine after nasal administration.
Zihe Yang, Linjie Li, Bin Deng, Yusen Xu, Yujing Du, Yongning Lv, Xuejia Zhai
Journal of Pharmaceutical and Biomedical Analysis October 15, 2025 DOI: 10.1016/j.jpba.2025.116945 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Observational study Peer reviewed |
|---|---|
| Population | Rats |
| Intervention | Ketamine |
| Dose | 84 mg |
| Topics | Ketamine Esketamine |
| Keywords | Brain region distribution Hplc-ms/ms Intranasal administration Pharmacokinetics Ketamine therapy Depression treatment Brain pharmacology Rapid-acting antidepressants Intranasal drug delivery |
| Citations | 3 |
| Key findings | After intranasal administration, ketamine rapidly reaches peak concentration in rat plasma at 5 minutes and distributes most highly in the kidneys and liver, while in the brain it concentrates primarily in the hypothalamus and hippocampus. |
Abstract
Major depressive disorder is a severe mental condition characterized by abnormalities in the structure and function of the brain. Ketamine is a novel antidepressant that has rapid effects on depression. This drug is clinically used to treat depression in patients with acute suicidal ideation or behavior. It is typically administered at a dose of 84 mg. However, the distribution of ketamine in the body after intranasal administration, particularly in the brain, remains unknown. In the present study, we utilized a high-performance liquid chromatography-tandem mass spectrometry method to measure ketamine concentrations in rat plasma and several tissues. The measurement ranges were 5-8000 ng/mL for the plasma samples and 5-5000 ng/mL for the tissue samples. The pharmacokinetic profile revealed that the rat plasma ketamine concentration rapidly spiked to a peak of 8002 ng/mL within about 5 min, followed by a rapid decline, nearly reaching 0 ng/mL by about 3 h; the half-life was 27 min. Tissue distribution results revealed that ketamine concentrations in different tissues peaked at 5 min. The highest concentration was noted in the kidneys, followed by the liver. In the rat brain regions, ketamine was primarily concentrated in the hypothalamus and hippocampus, with lower concentrations in the striatum and prefrontal cortex. Our novel methodological approach and findings provide a significant theoretical foundation for using ketamine in clinical settings.
Comparable studies
Other preclinical and animal studies on ketamine, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| mTOR-Dependent Synapse Formation Underlies the Rapid Antidepressant Effects of NMDA Antagonists Rats | 2010 | Observational study | |
| Activation of Glutamatergic Neurotransmission by Ketamine: A Novel Step in the Pathway from NMDA Receptor Blockade to Dopaminergic and Cognitive Disruptions Associated with the Prefrontal Cortex Conscious rats | 1997 | Dose-response study with microdialysis and behavioral testing | |
| NMDAR inhibition-independent antidepressant actions of ketamine metabolites Mice | 2016 | Preclinical study | |
| The dissociative anaesthetics, ketamine and phencyclidine, selectively reduce excitation of central mammalian neurones by N‐methyl‐aspartate Spinal neurons in decerebrate or pentobarbitone-anaesthetized cats and rats | 1983 | Experimental study | |
| R-ketamine: a rapid-onset and sustained antidepressant without psychotomimetic side effects Mice | 2015 | Experimental study |
Citations in the library
Cited by 2
- Intranasal Ketamine Alleviates Depressive-like Behaviors in Chronic Unpredictable Mild Stress Rats in Association with Hypothalamic NADH:Ubiquinone Oxidoreductase Subunit A10. European Journal of Pharmacology July 19, 2026
- Impact of subanesthetic ketamine delivered via AmyloLipid nanovesicle (ALN)-based intranasal system on biobehavioral responses in an animal model of PTSD Translational Psychiatry March 25, 2026
Cites 9
- Efficacy and Safety of Flexibly Dosed Esketamine Nasal Spray Combined With a Newly Initiated Oral Antidepressant in Treatment-Resistant Depression: A Randomized Double-Blind Active-Controlled Study American Journal of Psychiatry May 21, 2019
- Efficacy and Safety of Intranasal Esketamine for the Rapid Reduction of Symptoms of Depression and Suicidality in Patients at Imminent Risk for Suicide: Results of a Double-Blind, Randomized, Placebo-Controlled Study American Journal of Psychiatry April 16, 2018
- A Double-Blind, Randomized, Placebo-Controlled, Dose-Frequency Study of Intravenous Ketamine in Patients With Treatment-Resistant Depression American Journal of Psychiatry April 8, 2016
- Esketamine Nasal Spray for Rapid Reduction of Depressive Symptoms in Patients With Major Depressive Disorder Who Have Active Suicide Ideation With Intent: Results of a Phase 3, Double-Blind, Randomized Study (ASPIRE II) The International Journal of Neuropsychopharmacology August 26, 2020
- Esketamine Nasal Spray for Rapid Reduction of Major Depressive Disorder Symptoms in Patients Who Have Active Suicidal Ideation With Intent The Journal of Clinical Psychiatry May 11, 2020
and 4 more in the library