In vitro and in vivo assessment of the abuse potential of PF614, a novel BIO-MD™ prodrug of oxycodone

Abstract

The Bio-Activated Molecular Delivery prodrug design limits the use of PF614 to the intended oral route of delivery with reduced potential for IV or nasal abuse, as it cannot be activated intravenously or nasally to provide an active opioid. Unlike existing opioid formulations, the extended-release profile of PF614 cannot be accelerated by chewing or ex vivo extraction to pharmacologically active substances.

Clinical evaluation of PF614, a novel TAAP prodrug of oxycodone, versus OxyContin in a multi‐ascending dose study with a bioequivalence arm in healthy volunteers

“…Early proof‐of‐concept efforts with TAAP technology focused on PF329, an AD prodrug of hydromorphone that had an extended‐release profile 7 . Our lead TAAP product in clinical development is PF614, a prodrug of oxycodone 8 . Following ingestion of PF614, activation of oxycodone release from PF614 proceeds via a two‐step process including (i) trypsin activation via metabolism in the small intestine and (ii) a subsequent intramolecular cyclization‐release reaction (Figure S1).…”

“… 7 Our lead TAAP product in clinical development is PF614, a prodrug of oxycodone. 8 Following ingestion of PF614, activation of oxycodone release from PF614 proceeds via a two‐step process including (i) trypsin activation via metabolism in the small intestine and (ii) a subsequent intramolecular cyclization‐release reaction (Figure S1 ). The trypsin activation produces a nucleophilic amine intermediate PFR06082 and L‐arginine‐glycine‐N‐malonate (PFR06112).…”