Triglyceride-Mimetic Prodrugs of Buprenorphine Enhance Oral Bioavailability via Promotion of Lymphatic Transport.

ABSTRACT: Buprenorphine (BUP) is a potent opioid analgesic that is widely used for severe pain management and opioid replacement therapy. The oral bioavailability of BUP, however, is significantly limited by first-pass metabolism. Previous studies have shown that triglyceride (TG) mimetic prodrugs of the steroid hormone testosterone circumvent first-pass metabolism by directing drug transport through the intestinal lymphatics, bypassing the liver. The current study expanded this prodrug strategy to BUP. Here different self-immolative (SI) linkers were evaluated to conjugate BUP to the 2 position of the TG backbone via the phenol group on BUP. The SI linkers were designed to promote drug release in plasma. Lipolysis of the prodrug in the intestinal tract was examined via incubation with simulated int

SUBMITTER: Quach T 

PROVIDER: S-EPMC9039622 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature