Metabolism and metabolomics of ketamine: a toxicological approach
Ricardo Dinis-Oliveira
Forensic Sciences Research January 2, 2017 DOI: 10.1080/20961790.2017.1285219 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Review Peer reviewed |
|---|---|
| Topics | Esketamine Ketamine |
| Citations | 2 |
| Key findings | Ketamine is metabolized via cytochrome P450 into norketamine and other metabolites, and metabolomics reveals it alters several biological pathways including glycolysis and amino acid metabolism. |
Abstract
ABSTRACT Ketamine is a phencyclidine derivative and a non-competitive antagonist of N-methyl-D-aspartate (NMDA) receptor for which glutamate is the full agonist. It produces a functional dissociation between the thalamocortical and limbic systems, a state that has been termed as dissociative anaesthesia. Considerable variability in the pharmacokinetics and pharmacodynamics between individuals that can affect dose-response and toxicological profile has been reported. This review aims to discuss pharmacokinetics of ketamine, namely focusing on all major and minor, active and inactive metabolites. Both ketamine optical isomers undergo hepatic biotransformation through the cytochrome P450, specially involving the isoenzymes 3A4 and 2B6. It is first N-demethylated to active metabolite norketamine. Different minor pathways have been described, namely hydroxylation of the cyclohexanone ring of ketamine and norketamine, and further conjugation with glucuronic acid to increase renal excretion. More recently, metabolomics data evidenced the alteration of several biological pathways after ketamine administration such as glycolysis, tricarboxylic acid cycle, amino acids metabolism and mitochondrial β-oxidation of fatty acids. It is expected that knowing the metabolism and metabolomics of ketamine may provide further insights aiming to better characterize ketamine from a clinical and forensic perspective.
Comparable studies
Other narrative reviews on ketamine, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Ketamine and Ketamine Metabolite Pharmacology: Insights into Therapeutic Mechanisms | 2018 | Review | |
| Mechanisms of Ketamine Action as an Antidepressant | 2018 | Review | |
| Synthesizing the Evidence for Ketamine and Esketamine in Treatment-Resistant Depression: An International Expert Opinion on the Available Evidence and Implementation Adults with treatment-resistant depression | 2021 | Review | |
| Ketamine Pharmacology: An Update (Pharmacodynamics and Molecular Aspects, Recent Findings) | 2013 | Review | |
| A Consensus Statement on the Use of Ketamine in the Treatment of Mood Disorders | 2017 | Review and consensus statement |
Citations in the library
Cited by 42
- Ketamine and Ketamine Metabolite Pharmacology: Insights into Therapeutic Mechanisms Pharmacological Reviews June 26, 2018
- Pharmacokinetic and Pharmacodynamic Aspects of Peyote and Mescaline: Clinical and Forensic Repercussions Current Molecular Pharmacology October 15, 2018
- The Psychedelic Future of Post-Traumatic Stress Disorder Treatment Current Neuropharmacology January 5, 2024
- The clinical toxicology of ketamine Clinical Toxicology June 2, 2023
- Efficacy and Safety of Intranasal Esketamine in Patients With Treatment-Resistant Depression and Comorbid Chronic Post-traumatic Stress Disorder: Open-Label Single-Arm Pilot Study Frontiers in Psychiatry July 8, 2022
and 37 more in the library
Cites 19
- mTOR-Dependent Synapse Formation Underlies the Rapid Antidepressant Effects of NMDA Antagonists Science August 19, 2010
- Synaptic Dysfunction in Depression: Potential Therapeutic Targets Science October 4, 2012
- Ketamine Pharmacology: An Update (Pharmacodynamics and Molecular Aspects, Recent Findings) CNS Neuroscience & Therapeutics April 10, 2013
- Use and efficacy of low-dose ketamine in the management of acute postoperative pain: a review of current techniques and outcomes Pain August 1, 1999
- Ketamine for chronic pain: risks and benefits British Journal of Clinical Pharmacology February 21, 2013
and 14 more in the library