Pharmacokinetics of xylazine and fentanyl in patients presenting to the emergency department after non-fatal opioid overdose.

Abstract

Xylazine is an alpha-2 agonist found as an adulterant in illicitly-manufactured fentanyl. Little information is available about its pharmacokinetics in humans. We conducted a naturalistic study with thirteen adult patients presenting to two urban, tertiary care emergency departments for suspected opioid overdose and concomitant xylazine exposure. This study was conducted at two US emergency departments in Worcester, MA. Serial blood specimens were collected over 4h at 30-60min intervals for pharmacokinetic analyses. We developed a quantitative analytical method to measure the blood concentration of xylazine and its metabolites, fentanyl and its metabolite, and medetomidine and its metabolite. All thirteen participants had detectable concentrations of xylazine and fentanyl in their blood; five participants also had medetomidine present. Initial blood concentrations (mean±SD, ng/mL) were 47 ± 53 for xylazine, 14 ± 15 for fentanyl, 23 ± 19 for norfentanyl, and 25 ± 24 for medetomidine. Data from a subset of eight participants were used to calculate drug half-lives (t_1/2) (mean±SD, min): 345 ± 145 for xylazine and 537 ± 451 for fentanyl. The elimination t_1/2 of xylazine in these opioid overdose participants was considerably longer than predicted from veterinary data. The fentanyl t_1/2 values were within the upper range reported in the literature. Understanding the pharmacokinetics of xylazine is vital for projecting outcomes of xylazine exposed patients and could allow for improved interpretation in forensic analyses. The quantitative assay we developed for xylazine and its metabolites is suitable for clinical research.