The scientific study examines the pharmacokinetics of xylazine, a veterinary sedative increasingly detected in illicit drug supplies, especially in combinations with fentanyl. Researchers aimed to quantify how long xylazine remains in human plasma and investigate its metabolites. This work offers significant implications for understanding overdose risks, treatment strategies, and the detection of xylazine in clinical and forensic settings.
Xylazine has been identified in the illicit drug supply under street names such as "tranq" and "horse anesthesia." While developed as an antihypertensive agent, its adverse effects, including severe central nervous system depression and hypotension, prevented its approval for human use.
Recently, its association with fentanyl-related overdose deaths has surged. Between 2019 and 2022, a 276% increase in xylazine detection in such cases was reported. Despite its rising prevalence, the metabolism and elimination of xylazine in humans remain poorly understood, presenting challenges in clinical and forensic toxicology.
This study analyzed plasma samples from 28 patients using liquid chromatography-tandem mass spectrometry (LC-MS/MS) to determine xylazine’s half-life and detect metabolites. Patients were chosen based on the presence of xylazine during urine drug screening. The median terminal half-life of xylazine was 12 hours, with a range between 5.9 to 20.8 hours, significantly longer than previously observed in animal studies.
Two key metabolites, oxo-xylazine and sulfone-xylazine, were detected in all plasma specimens containing xylazine. These metabolites were found to persist in plasma as long as the parent compound, suggesting their relevance in the pharmacological effects and detection windows of xylazine.
The results highlight that xylazine's extended half-life in humans, compared to earlier findings, underscores the drug's lingering presence and potential prolonged effects when combined with fentanyl. This persistence may partly explain the reports of extended sedation and other severe health consequences among users. Additionally, the detection of oxo-xylazine and sulfone-xylazine as primary metabolites enhances the understanding of xylazine metabolism in humans, providing a basis for more precise forensic analysis and possible therapeutic interventions.
The study acknowledges limitations, including the small sample size and lack of information on dosages or exact timing of xylazine administration. Variations in elimination rates might stem from factors such as administration routes, patient health conditions, or repeated exposures.
The prolonged half-life of xylazine and its detectable metabolites provide essential information for designing drug monitoring programs and developing tailored treatments for affected individuals.
The full study can be accessed for detailed insights and methodology through the journal Clinical Chemistry: https://doi.org/10.1093/clinchem/hvae163 (clearnet).
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