by Association for Diagnostic and Laboratory Medicine (ADLM (formerly AACC))

Structure of xylazine and metabolites. N-(2,6-diemthylphenyl) thiourea and 2,6-dimethylaniline were not identified in this study but previously reported. Credit: Clinical Chemistry (2024). DOI: 10.1093/clinchem/hvae163

A novel study published in the journal, Clinical Chemistry, has found that it takes the human body much longer than previously thought to clear xylazine—one of the most popular emerging drugs of abuse in the U.S. This much-needed insight into how the body processes xylazine could improve treatment of overdose patients who’ve taken it.

Xylazine has traditionally been used in veterinary practice as a tranquilizer, but between 2019 and 2022, detection of xylazine in fentanyl-associated overdose deaths soared by 276%, according to a report from the Centers for Disease Control and Prevention. This is particularly concerning because, since xylazine’s not an opioid, Narcan doesn’t work in reviving people who’ve taken it.

Complicating matters further is the fact that xylazine has been studied very little in humans, which means that health care providers don’t have all the information they need to treat patients who’ve used it.

In an effort to help close this gap in knowledge about the drug, a team of researchers led by Bridgit Crews, Ph.D., associate professor of pathology and immunology at the Washington University School of Medicine in St. Louis, set out to determine how long xylazine remains in the body. The team initially identified 493 patients who’d used xylazine, nearly all of whom also tested positive for fentanyl.

Of these, 28 met the study criteria and had blood samples available that could be used to assess xylazine’s half-life, which is the amount of time it takes for the blood concentration of a drug to drop to half of its initial amount. To estimate xylazine’s half-life, the researchers analyzed the blood samples and plotted the concentration of xylazine in the blood over time.

The results showed that the average half-life of xylazine in the blood is 12 hours, which is longer than that found in several animal species and in a single human case study that showed a half-life of nearly 5 hours in the blood. This suggests that xylazine stays in the human body for up to 2 days after an individual’s last exposure, depending on the amount ingested.

Additionally, the team identified metabolites—substances produced during the body’s breakdown of a drug—that could help improve identification of xylazine in future studies, as well as clinical testing for the drug.

“There is scarce information on the pharmacokinetics of xylazine in humans, particularly in those who may chronically use fentanyl mixed with xylazine,” Crews said.

“A better understanding of typical xylazine concentrations encountered in individuals who use fentanyl mixed with xylazine, as well as the duration that xylazine remains detectable in blood, may help to improve the interpretation of clinical studies, provide evidence to support appropriate cutoffs for xylazine surveillance, and potentially inform treatment and/or patient monitoring or risk mitigation strategies.”

More information: Yanchun Lin et al, Xylazine Pharmacokinetics in Patients Testing Positive for Fentanyl and Xylazine, Clinical Chemistry (2024). DOI: 10.1093/clinchem/hvae163

Journal information:Clinical Chemistry

Provided by Association for Diagnostic and Laboratory Medicine (ADLM (formerly AACC))

---

Explore further

Xylazine increasingly identified in illicitly manufactured fentanyl overdose deaths