Buprenorphine maintenance and mu-opioid receptor availability in the treatment of opioid use disorder: Implications for clinical use and policy

Background: Sublingual formulations of buprenorphine (BUP) and BUP/naloxone have well-established pharmacokinetic and pharmacodynamic profiles, and are safe and effective for treating opioid use disorder. Since approvals of these formulations, their clinical use has increased. Yet, questions have arisen as to how BUP binding to mu-opioid receptors (mu ORs), the neurobiological target for this medication, relate to its clinical application. BUP produces dose- and time-related alterations of mu OR availability but some clinicians express concern about whether doses higher than those needed to prevent opioid withdrawal symptoms are warranted, and policymakers consider limiting reimbursement for certain BUP dosing regimens. Methods: We review scientific data concerning BUP-induced changes in mu OR availability and their relationship to clinical efficacy. Results: Withdrawal suppression appears to require <= 50% mu OR availability, associated with SUP trough plasma concentrations >= 1 ng/mL; for most patients, this may require single daily BUP doses of 4 mg to defend against trough levels, or lower divided doses. Blockade of the reinforcing and subjective effects of typical doses of abused opioids require <20% mu OR availability, associated with BUP trough plasma concentrations >= 3 ng/mL; for most individuals, this may require single daily BUP doses >16 mg, or lower divided doses. For individuals attempting to surmount this blockade with higher-than-usual doses of abused opioids, even larger BUP doses and <10% mu OR availability would be required. Conclusion: For these reasons, and given the complexities of studies on this issue and comorbid problems, we conclude that fixed, arbitrary limits on BUP doses in clinical care or limits on reimbursement for this care are unwarranted. (C) 2014 Elsevier Ireland Ltd. All rights reserved.