Buprenorphine Duration of Action: Mu-opioid Receptor Availability and Pharmacokinetic and Behavioral Indices

Background Buprenorphine (BUP) is effective in the treatment of opioid dependence when given on alternating days, probably as a result of long-lasting occupation of μ opioid receptors (μORs). This study examined the duration of action of BUP at μORs and correlations with pharmacokinetic and pharmacodynamic outcomes in 10 heroin-dependent volunteers. Methods Availability of μOR (measured with positron emission tomography and [11C]-carfentanil), plasma BUP concentration, opioid withdrawal symptoms, and blockade of hydromorphone (HYD; heroin-like agonist) effects were measured at 4, 28, 52, and 76 hours after omitting the 16 mg/d dose of BUP in a study reported elsewhere. Results Relative to heroin-dependent volunteers maintained on BUP placebo, whole-brain μOR availability was 30%, 54%, 67%, and 82% at 4, 28, 52, and 76 hours after BUP. Regions of interest showed similar effects. Plasma concentrations of BUP were time dependent, as were withdrawal symptoms, carbon dioxide sensitivity and extent of HYD blockade. Availability of μOR was also correlated with BUP plasma concentration, withdrawal symptoms, and HYD blockade. Conclusions Together with our previous findings, it appears that μOR availability predicts changes in pharmacokinetic and pharmacodynamic measures and that about 50%–60% BUP occupancy is required for adequate withdrawal symptom suppression (in the absence of other opioids) and HYD blockade.