Plasma Carbamazepine and Carbamazepine-Epoxide Concentrations as Indicators of Consciousness Impairment in Acute Poisoning: A Sex-Based Analysis.

BACKGROUND: Carbamazepine (CBZ) is a widely used antiepileptic drug with a narrow therapeutic window. Its potential for severe toxicity in overdose is primarily due to its active metabolite, carbamazepine-10,11-epoxide (CBZ-E). In acute CBZ intoxication, sex-specific differences and toxicokinetics are poorly understood, especially the impact on neurological impairment, despite its clinical relevance. OBJECTIVES: The present study aimed to explore the clinical, biochemical, and toxicokinetic data of patients with acute CBZ poisoning to assess the relationship between CBZ exposure and the level of consciousness upon hospital admission and stay and to identify potential sex-based differences in the course and severity of poisoning to develop individualised clinical management strategies for these patients. METHODS: We conducted a retrospective observational study of 99 adult patients admitted to a national toxicology centre with confirmed acute CBZ poisoning from January 2012 to December 2022. Plasma concentrations of CBZ and CBZ-E were measured using high-performance liquid chromatography. Clinical and biochemical data were analysed regarding sex and level of consciousness on admission and throughout the hospital stay. RESULTS: There were no significant differences between sexes in ingested dose and CBZ initial and peak concentrations. Women exhibited significantly higher peak CBZ-E concentrations and CBZ-E/CBZ ratios, which may be associated with a nonsignificant trend toward longer hospital stay. Men had higher baseline haematological and biochemical parameters, consistent with known physiological differences. Females more frequently required dopamine support for hypotension, while head injuries occurred exclusively in males. A strong dose-response relationship was observed between CBZ and CBZ-E exposure and impaired consciousness. Multivariate regression analysis confirmed that both CBZ and CBZ-E Cmax were independent predictors of consciousness impairment, with CBZ-E Cmax showing a slightly stronger association than the parent drug. CONCLUSIONS: Early toxicokinetic assessment is clinically important in acute CBZ poisoning, particularly considering the significant sex-related differences in CBZ metabolism and toxicity. Monitoring the active metabolite CBZ-E may provide additional clinical value, especially in female patients. CBZ and CBZ-E plasma concentrations are valuable biomarkers of poisoning severity.