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J Pharmacol Exp Ther. 2018 May;365(2):346-353. doi: 10.1124/jpet.117.247049. Epub 2018 Mar 13.

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

Author information

1
Minneapolis Medical Research Foundation, Minneapolis, Minnesota (M.D.R., M.L., F.B., S.J.P., P.R.P., M.P.); University of Minnesota College of Pharmacy, Minneapolis, Minnesota (M.J.R., A.K.B.); Research Triangle Institute, Research Triangle Park, North Carolina (F.I.C., S.P.R.); Winston Biopharmaceutical Consulting, Boulder, Colorado (S.W.); and University of Minnesota Medical School (P.R.P., M.P.), and Center for Immunology (M.P.), University of Minnesota, Minneapolis, Minnesota rale0011@umn.edu.
2
Minneapolis Medical Research Foundation, Minneapolis, Minnesota (M.D.R., M.L., F.B., S.J.P., P.R.P., M.P.); University of Minnesota College of Pharmacy, Minneapolis, Minnesota (M.J.R., A.K.B.); Research Triangle Institute, Research Triangle Park, North Carolina (F.I.C., S.P.R.); Winston Biopharmaceutical Consulting, Boulder, Colorado (S.W.); and University of Minnesota Medical School (P.R.P., M.P.), and Center for Immunology (M.P.), University of Minnesota, Minneapolis, Minnesota.

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 + 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.

PMID:
29535156
PMCID:
PMC5884377
[Available on 2019-05-01]
DOI:
10.1124/jpet.117.247049

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