Opioid dose-And route-dependent efficacy of oxycodone and heroin vaccines in rats

Michael D. Raleigh, Megan Laudenbach, Federico Baruffaldi, Samantha J. Peterson, Michaela J. Roslawski, Angela K Birnbaum, F. Ivy Carroll, Scott P. Runyon, Scott Winston, Paul R Pentel, Marco Pravetoni

Research output: Contribution to journalArticlepeer-review

16 Scopus citations

Abstract

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 1 6-AM 1 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 OXYKLH 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.

Original languageEnglish (US)
Pages (from-to)346-353
Number of pages8
JournalJournal of Pharmacology and Experimental Therapeutics
Volume365
Issue number2
DOIs
StatePublished - May 2018

Bibliographical note

Funding Information:
This work was supported by the National Institutes of Health National Institute on Drug Abuse [Grant U01DA038876] (to M.P. and P.R.P.). https://doi.org/10.1124/jpet.117.247049. s This article has supplemental material available at jpet.aspetjournals.org.

Publisher Copyright:
© 2018 by The American Society for Pharmacology and Experimental Therapeutics.

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