Abstract
Development of opioid vaccines to prevent overdose is an active area of research. The protective efficacy of these vaccines depends on vaccine-induced antibodies (Ab) that bind to opioids with high affinity and targeted specificity. Because Ab performance is ultimately constrained by the in vivo behavior of the drug, and clinically relevant peak blood concentrations Cmax associated with lethal opioid overdose are undefined, a clear understanding of opioid pharmacokinetics in humans is essential for rational vaccine design, preclinical modeling, and interpretation of clinical results. The purpose of this review is to summarize available data on key PK parameters of opioid analogues in humans to a) facilitate establishment of Ab correlates of protection during opioid vaccine development and testing and b) assess Ab cross-reactivity to off-target opioid agonists and antagonists. Lastly, we discuss their utility in informing design and interpretation of preclinical and clinical studies of opioid vaccines and protective therapeutics.