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November 21, 2025Frontiers in PharmacologyOpen Access

Preclinical pharmacokinetic characterization of (R)-ketamine injection, a novel antidepressant glutamatergic agent

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Authors

RWRui WangYJYongchao JinBZBingjie Zou

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Overview

Preclinical research shows (R)-ketamine improves depressive symptoms in animal models, indicating its potential as a novel antidepressant.

Key Points

  • Investigate the pharmacokinetic behavior of (R)-ketamine to support its development for human use.
  • Conducted single- and multiple-dose pharmacokinetic studies in rats and Beagle dogs.
  • Performed tissue distribution studies in Sprague-Dawley rats.
  • Carried out in vitro metabolism studies using microsomes from various species.
  • Used elution studies in rats to understand elimination pathways.
  • Employed allometric scaling to predict human plasma clearance.
  • Demonstrated nonlinear pharmacokinetics in SD rats and Beagle dogs during intravenous administration.
  • Identified significant tissue distribution in fat and kidneys of rats.
  • Showed (R)-ketamine effectively penetrates the blood-brain barrier with a brain/plasma ratio of 2.25.
  • Primary elimination pathway is metabolic, with predominant metabolites identified in liver microsomes.

Cite This Study

Wang et al. (2025) studied this question.

synapsesocial.com/papers/6924e3f2c0ce034ddc34f193https://doi.org/10.3389/fphar.2025.1699304
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Also Consider

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  1. 1(R)-(-)-Ketamine: The Promise of a Novel Treatment for Psychiatric and Neurological Disorders2024 · 29 citations
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  5. 5Ketamine metabolism via hepatic CYP450 isoforms contributes to its sustained antidepressant actions2024