ArticleAnesthesiology2016
Role of Cytochrome P4502B6 Polymorphisms in Ketamine Metabolism and Clearance.
Article in Anesthesiology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
28 citing papers in PubMed, 61 citations in OpenAlex.
- The role of cytochrome P450 polymorphisms in the pharmacokinetics of oral esketamine.The pharmacogenomics journal · 2026Trial
- Stereoselective ketamine effect on cardiac output: a population pharmacokinetic/pharmacodynamic modelling study in healthy volunteers.British journal of anaesthesia · 2021Trial
- Common Polymorphisms of CYP2B6 Influence Stereoselective Bupropion Disposition.Clinical pharmacology and therapeutics · 2019Trial
- Pharmacokinetics and Safety of a Single Subcutaneous or Intramuscular Dose of Ketamine in Healthy Horses.Journal of veterinary pharmacology and therapeutics · 2026Article
- Metabolic patterns of new psychoactive substances: Methyl-ketamine and 2-oxo-PCE in rats using UHPLC-QTOF analysis.Forensic science international. Synergy · 2025Article
- Esketamine in depression: putative biomarkers from clinical research.European archives of psychiatry and clinical neuroscience · 2025Review
- Ketamine-From an Anesthetic to a Psychiatric Drug: Mechanisms of Action, Clinical Applications and Potential Risks.Molecules (Basel, Switzerland) · 2025Review
- HumanFrontiers in neuroscience · 2025Article
- Pharmacokinetics and Safety of Fospropofol Disodium for Injection in Subjects with Hepatic Impairment Compared with Healthy Matched Controls: A Prospective Cohort Study.Drug design, development and therapy · 2025Article
- Ketamine in neuropsychiatric disorders: an update.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2024Review
- Cerebrospinal fluid exploratory proteomics and ketamine metabolite pharmacokinetics in human volunteers after ketamine infusion.iScience · 2023Article
- The antidepressant actions of ketamine and its enantiomers.Pharmacology & therapeutics · 2023Review
- Arylcyclohexylamine Derivatives: Pharmacokinetic, Pharmacodynamic, Clinical and Forensic Aspects.International journal of molecular sciences · 2022Review
- Possible Use of Minocycline in Adjunction to Intranasal Esketamine for the Management of Difficult to Treat Depression following Extensive Pharmacogenomic Testing: Two Case Reports.Journal of personalized medicine · 2022Article
- Sex Differences in the Behavioral, Molecular, and Structural Effects of Ketamine Treatment in Depression.The international journal of neuropsychopharmacology · 2022Review
- Targeting Affective Mood Disorders With Ketamine to Prevent Chronic Postsurgical Pain.Frontiers in pain research (Lausanne, Switzerland) · 2022Review
- Historical Pathways for Opioid Addiction, Withdrawal with Traditional and Alternative Treatment Options with Ketamine, Cannabinoids, and Noribogaine: A Narrative Review.Health psychology research · 2022Article
- Interrogating in vivo T-cell metabolism in mice using stable isotope labeling metabolomics and rapid cell sorting.Nature protocols · 2021Article
- Hydroxynorketamines: Pharmacology and Potential Therapeutic Applications.Pharmacological reviews · 2021Review
- Ketamine: The final frontier or another depressing end?Behavioural brain research · 2020Review
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Authors and funding
4 authors at 1 institution in 3 countries.
Funding
Abstract
backgroundAt therapeutic concentrations, cytochrome P4502B6 (CYP2B6) is the major P450 isoform catalyzing hepatic ketamine N-demethylation to norketamine in vitro. The CYP2B6 gene is highly polymorphic. The most common variant allele, CYP2B6*6, is associated with diminished hepatic CYP2B6 expression and catalytic activity compared with wild-type CYP2B6*1/*1. CYP2B6.6, the protein encoded by the CYP2B6*6 allele, and liver microsomes from CYP2B6*6 carriers had diminished ketamine metabolism in vitro. This investigation tested whether humans with the CYP2B6*6 allele would have decreased clinical ketamine metabolism and clearance.
methodsThirty volunteers with CYP2B6*1/*1, *1/*6, or *6/*6 genotypes (n = 10 each) received a subsedating dose of oral ketamine. Plasma and urine concentrations of ketamine and the major CYP2B6-dependent metabolites were determined by mass spectrometry. Subjects' self-assessment of ketamine effects were also recorded. The primary outcome was ketamine N-demethylation, measured as the plasma norketamine/ketamine area under the curve ratio. Secondary outcomes included plasma ketamine enantiomer and metabolite area under the plasma concentration-time curve, maximum concentrations, apparent oral clearance, and metabolite formation clearances.
resultsThere was no significant difference between CYP2B6 genotypes in ketamine metabolism or any of the secondary outcome measures. Subjective self-assessment did reveal some differences in energy and level of awareness among subjects.
conclusionsThese results show that while the CYP2B6*6 polymorphism results in diminished ketamine metabolism in vitro, this allelic variant did not affect single, low-dose ketamine metabolism, clearance, and pharmacokinetics in vivo. While in vitro drug metabolism studies may be informative, clinical investigations in general are needed to validate in vitro observations.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.