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 via PubMed
Summary
AI-generated from the abstractAfter intranasal administration in rats, ketamine rapidly enters the bloodstream, reaching a peak concentration of 8002 ng/mL within about 5 minutes, then declines to near zero by about 3 hours, with a half-life of 27 minutes. Tissue analysis shows the highest ketamine levels in the kidneys, followed by the liver. Within the brain, ketamine concentrates most in the hypothalamus and hippocampus, with lower amounts in the striatum and prefrontal cortex. These findings clarify how ketamine distributes throughout the body and brain after intranasal delivery, providing a basis for understanding its clinical use in treating depression.
Study at a glance
| Characteristics | Observational study Peer reviewed |
|---|---|
| Population | Rats |
| Intervention | Ketamine |
| Dose | 84 mg |
| Topics | Ketamine |
| Keywords | Brain region distribution Hplc-ms/ms Intranasal administration Pharmacokinetics Ketamine therapy |
| Citations | 3 |
| Key finding | 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.