Biotransformation of ketamine in terminal in vivo experiments under chronic intermittent hypoxia conditions and the role of AhR.
Archives of toxicology April 19, 2025 António B Pimpão, Luísa Teixeira-Santos, Nuno R Coelho et al.
Chronic intermittent hypoxia (CIH), which models the low-oxygen episodes of obstructive sleep apnea, alters how the body processes ketamine, a common anesthetic. In rats exposed to CIH, a shift in ketamine metabolism favored hydroxynorketamine over norketamine in liver and kidney tissues. Six metabolites were identified, including the first report of norketamine glucuronide formation in the liver. Blocking the aryl hydrocarbon receptor (AhR) with an antagonist changed hydroxynorketamine glucuronidation, suggesting AhR overactivation in CIH influences ketamine breakdown. These findings highlight that anesthetic metabolism can differ under disease conditions like sleep apnea, emphasizing the need to account for such changes in metabolic studies.