The Effect of a Multivalent Vaccine on the Pharmacokinetics of Opioids in a Polydrug Scenario in Rats

Abstract ID 100637 Poster Board 287 More than 100,000 cases of fatal drug overdose are reported annually, with approximately 70% involving opioids. Synthetic opioids, such as fentanyl and its analogs, are the leading cause of fatal overdoses. Individuals with opioid use disorder (OUD) and substance use disorders (SUD) often self-administer polydrug street mixtures that contain multiple opioids (i.e., fentanyl with oxycodone and heroin), leading to poor survival outcomes. Our group has previously shown that active immunization with a quadrivalent opioid vaccine protects against the effects of a mixture of fentanyl, carfentanil, oxycodone, and heroin in preclinical models. These vaccines consist of haptens conjugated to immunogenic carrier proteins, and adsorbed or admixed on adjuvants. These vaccines induce a T-cell-dependent B cell response that generates drug-specific polyclonal antibodies that of hapten-specific antibodies. bind to target drugs, sequestering them in the bloodstream, and prevent drug distribution to the brain. In a polydrug scenario, alteration of pharmacokinetic (PK) parameters of target drugs after the vaccination remains unknown. Here, Sprague Dawley rats (n = 3/group) were immunized with control, fentanyl vaccine, or quadrivalent vaccine targeting fentanyl, carfentanil, oxycodone, and heroin. Jugular vein cannulation was performed to collect blood samples over time following a drug challenge. The study determined the impact of polydrug usage on fentanyl PK by comparing scenarios involving fentanyl alone with those involving fentanyl combined with carfentanil, oxycodone, and heroin. Furthermore, the study demonstrated that vaccination decreases the absorption rate constant (ka) and drug clearance (CL) of the target opioids. This work was supported by the National Institute on Drug Abuse Grants UG3DA048386