Tyler Dunlap, Pharm.D., DABCP¹, Hillary Husband, Ph.D.², Sara Miller, Pharm.D.¹, Alyssa Tilhou, MD, Ph.D.³
¹Metrum Research Group, Boston, MA, USA, ²Louisiana Tech University, Ruston, LA, USA, ³Boston University, Boston, MA, USA
Presented at the 2026 Annual Meeting of the American College of Clinical Pharmacology (ACCP 2026), on September 28, 2026.
Opioid use disorder (OUD) is a chronic relapsing condition characterized by compulsive use of opioids, such as fentanyl, despite significant harms. While buprenorphine, a Mu-opioid receptor (MOR) partial agonist, can effectively stabilize individuals with OUD, withdrawal during induction [due to underdosing or displacement of full agonist opioids (“precipitated withdrawal”)] often leads to treatment discontinuation. Alternative buprenorphine induction strategies have been proposed, but quantitative evidence informing their design is limited. This study introduces a quantitative medicine framework (QMF) to optimize two strategies: macrodosing, characterized by high-dose initiation of buprenorphine with abrupt cessation of nonprescribed opioids to achieve rapid therapeutic receptor occupancy (RO) and avoid underdosing; and microdosing, characterized by low-dose initiation and gradual titration of buprenorphine with continuation of nonprescribed opioids to mitigate risk for precipitated withdrawal.