Meeting report: DMDG peptide and oligonucleotide ADME workshop 2024

Area of Science:

• Pharmacology
• Drug Metabolism
• Biochemistry

Background:

• The 2024 Drug Metabolism and Discussion Group (DMDG) workshop convened experts to discuss critical challenges in the ADME (absorption, distribution, metabolism, and elimination) of peptide and oligonucleotide therapeutics.
• Peptide and oligonucleotide-based drugs represent a rapidly growing class of therapeutics, necessitating a deep understanding of their pharmacokinetic profiles.

Framework:

• The workshop focused on identifying and addressing key ADME challenges specific to peptides and oligonucleotides.
• Discussions covered metabolism of conjugated peptides and proteins, strategies for enhancing peptide metabolic stability, and drug metabolism and pharmacokinetic (DMPK) considerations for oligonucleotides.

Implementation:

• Key topics included in vitro metabolism studies, novel analytical techniques like hybridisation LC-MS/MS for oligonucleotide quantification, and imaging techniques for tracking oligonucleotide distribution.
• Strategies for increasing metabolic stability, identifying extrahepatic targets, and understanding metabolism and excretion were presented.
• The application of pharmacokinetic/pharmacodynamic (PKPD), physiologically based pharmacokinetic (PBPK), and modeling approaches were also discussed.

Implications:

• Addressing these ADME challenges is crucial for the successful development and clinical translation of novel peptide and oligonucleotide drugs.
• The insights gained will guide future research and development strategies, potentially accelerating the delivery of these advanced therapies to patients.
• This report summarizes the collective knowledge and innovative solutions presented, fostering further scientific discourse in the field.