Postdoctoral Fellow Johns Hopkins University Baltimore, Maryland, United States
Background:
Background: The opioid crisis is now driven by illicitly manufactured fentanyl (IMF). There is growing evidence that chronic IMF use has meaningful pharmacodynamic interactions with buprenorphine (BUP), an opioid use disorder (OUD) treatment. Therapeutic doses of fentanyl are sequestered into peripheral tissues; we postulate extended IMF clearance may contribute to BUP interactions and withdrawal presentation. This sub-study seeks to identify IMF and BUP concentrations, estimate IMF clearance, and explore the relationship between these and opioid withdrawal surrounding BUP induction.
Methods:
Methods: Participants presented for a 5-day residential, double-blind, placebo-controlled clinical trial of an orexin-receptor antagonist during BUP treatment (11/10/22 enrollment: 8/120) (parent trial NCT05145764). Individuals were eligible if they had moderate-to-severe OUD and were positive for fentanyl at screening and intake. Participants were maintained on short-acting opioids and managed symptomatically for 2-3 days before BUP induction. Throughout admission, both participant and observer-reported opioid withdrawal ratings were collected four times daily concurrent with capillary blood and urine. Plasma from capillary blood and urine will be quantified via LC-MS/MS for fentanyl, buprenorphine, and their primary metabolites norfentanyl and norbuprenorphine. Concentrations will be examined over time to estimate clearance and compared to opioid withdrawal ratings via regression analyses to explore IMF-BUP-withdrawal relationships.
NOVELTY OF DESIGN: Novelty of
Design: There are currently no pharmacokinetic studies of IMF in people with OUD, and no clear understanding of how IMF may interact with BUP or influence withdrawal. Pilot data will help inform future research and clinical practice.
