Opioid dose- and route-dependent efficacy of oxycodone and heroin vaccines in rats
Raleigh, M. D., Laudenbach, M., Baruffaldi, F., Peterson, S. J., Roslawski, M. J., Birnbaum, A. K., ... Pravetoni, M. (2018). Opioid dose- and route-dependent efficacy of oxycodone and heroin vaccines in rats. Journal of Pharmacology and Experimental Therapeutics. 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 (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.