ArticleArchives of toxicology2025
Biotransformation of ketamine in terminal in vivo experiments under chronic intermittent hypoxia conditions and the role of AhR.
Article in Archives of toxicology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
The trial behind it
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
0 citing papers in PubMed.
No citing paper in PubMed yet.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors.
Funding
Abstract
We were pioneers in describing aryl hydrocarbon receptor (AhR) activation by chronic intermittent hypoxia (CIH) in a rat pre-clinical model. This model mimics hypertension (HTN) secondary to obstructive sleep apnea, enabling longitudinal investigation of hypertension development. Concerns about the influence of barbiturates on AhR-regulated enzymes led us to opt for ketamine/medetomidine anesthesia in terminal in vivo experiments. However, the biotransformation and the metabolomic pathways of ketamine in CIH conditions, which is associated to AhR overactivation, are yet to be disclosed. A rat model of CIH was used, with experimental groups defined based on the duration of CIH exposure. Ketamine/medetomidine (75/0.5 mg/kg) was administered intraperitoneally as terminal anesthetic. Metabolomic strategies were used to reveal the profiles of ketamine and its metabolites in liver and kidney tissues, uncovering six metabolites, including the first report of norketamine glucuronide formation in the liver. While PCA analysis revealed similar ketamine metabolite fingerprints in normoxia and CIH, a predominance of hydroxynorketamine over norketamine was observed in CIH condition. A consistent association between norketamine, hydroxyketamine and the metabolome was found in both normoxia and CIH conditions. The AhR antagonist CH-223191 (5 mg/kg) influenced hydroxynorketamine glucuronidation in the liver. No changes in medetomidine biotransformation were detected. Overall, these findings expand the knowledge of ketamine metabolism and its tissue-dependence. The results emphasize the importance of considering how ketamine biotransformation may differ between control and experimental conditions in metabolic studies, particularly in chronic intermittent hypoxia conditions. The role of AhR in ketamine biotransformation is herein described for the first time.
Indexed as
Identifiers
What OpenQuestion holds
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.