Opioid Dose- and Route-Dependent Efficacy of Oxycodone and Heroin Vaccines in Rats

• Published in: The Journal of pharmacology and experimental therapeutics Vol. 365; no. 2; pp. 346 - 353
• Main Authors: Raleigh, Michael D, Laudenbach, Megan, Baruffaldi, Federico, Peterson, Samantha J, Roslawski, Michaela J, Birnbaum, Angela K, Carroll, F Ivy, Runyon, Scott P, Winston, Scott, Pentel, Paul R, Pravetoni, Marco
• Format: Journal Article
• Language: English
• Published: United States The American Society for Pharmacology and Experimental Therapeutics 01.05.2018
• Subjects: Drug Discovery and Translational Medicine
• ISSN: 0022-3565; 1521-0103
• DOI: 10.1124/jpet.117.247049

Heroin and oxycodone abuse occurs over a wide range of drug doses and by various routes of administration characterized by differing rates of drug absorption. The current study addressed the efficacy of a heroin vaccine [morphine hapten conjugated to keyhole limpet hemocyanin (M-KLH)] or oxycodone vaccine [oxycodone hapten conjugated to keyhole limpet hemocyanin (OXY-KLH)] for reducing drug distribution to brain after intravenous heroin or oxycodone, or subcutaneous oxycodone. Rats immunized with M-KLH or keyhole limpet hemocyanin (KLH) control received an intravenous bolus dose of 0.26 or 2.6 mg/kg heroin. Vaccination with M-KLH increased retention of heroin and its active metabolites 6-acetylmorphine (6-AM) and morphine in plasma compared with KLH controls, and reduced total opioid (heroin + 6-AM + morphine) distribution to brain but only at the lower heroin dose. Immunization also protected against respiratory depression at the lower heroin dose. Rats immunized with OXY-KLH or KLH control received 0.22 or 2.2 mg/kg oxycodone intravenously, the molar equivalent of the heroin doses. Immunization with OXY-KLH significantly reduced oxycodone distribution to brain after either oxycodone dose, although the magnitude of effect of immunization at the higher oxycodone dose was small (12%). By contrast, vaccination with OXY-KLH was more effective when oxycodone was administered subcutaneously rather than intravenously, reducing oxycodone distribution to brain by 44% after an oxycodone dose of 2.3 mg/kg. Vaccination also reduced oxycodone-induced antinociception. These data suggest that the efficacy of OXY-KLH and M-KLH opioid vaccines is highly dependent upon opioid dose and route of administration.