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J Pharmacol Exp Ther. 2018 Mar 13. pii: jpet.117.247049. doi: 10.1124/jpet.117.247049. [Epub ahead of print]

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

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Minneapolis Medical Research Foundation;
Minneapolis Medical Research Foundation.
University of Minnesota College of Pharmacy.
Research Triangle Institute.
Winston Biopharmaceutical Consulting.


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 (M-KLH) or oxycodone vaccine (OXY-KLH) for reducing drug distribution to brain after i.v. heroin or oxycodone, or s.c. oxycodone. Rats immunized with M-KLH or KLH control received an i.v. 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 to 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 i.v., 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 s.c. rather than i.v., reducing oxycodone distribution to brain by 44% after an oxycodone dose of 2.3 mg/kg. Vaccination also reduced oxycodone-induced antinociception. These data highlight the dependence of M-KLH and OXY-KLH vaccine efficacy on drug dose and route of administration, and help to understand the limits of their efficacy as well as how best to use them in humans.


antibodies; immunopharmacology; opioids; pharmacokinetics; respiratory pharmacology

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