Metabolism and Excretion of Therapeutic Peptides: Current Industry Practices, Perspectives, and Recommendations.

Therapeutic peptides (TPeps) have expanded from the initial endogenous peptides to complex modified peptides through medicinal chemistry efforts for almost a century. Different from small molecules and large proteins, the diverse submodalities of TPeps have distinct structures and carry different absorption, distribution, metabolism, and excretion (ADME) properties. There is no distinct regulatory guidance for the industry on conducting ADME studies (what, how, and when) for TPeps.

Meeting report: DMDG peptide and oligonucleotide ADME workshop 2022.

Challenges within peptide and oligonucleotide ADME (absorption, distribution, metabolism and elimination) and scientific ideas on how to solve them were presented and discussed at the DMDG (Drug Metabolism and Discussion Group) Peptide and Oligonucleotide ADME Workshop 2022 (2nd and 3rd of October 2022). This meeting report summarises the presentations and discussions from this workshop.The following topics were covered:Overview of the drug modality landscapeMetabolism & modellingAnalytical challengesDrug-drug interactions reports from industry working groupsRegulatory interactions.

Meeting report: oligonucleotide ADME workshop.

The current regulatory landscape for the development of oligonucleotide drugs may lead companies to perform a variety of small molecule-focussed absorption, distribution, metabolism and elimination (ADME) studies in support of filing packages. Asking the question, if the current activities are suitable for these modalities and should science-driven decisions on development of such molecules be implemented more in the industry.Challenges and opportunities within oligonucleotide ADME were presented and discussed at the online oligonucleotide ADME workshop (17th and 18th of November 2021).

Meeting report: 3rd workshop of the peptide ADME discussion group.

Challenges and opportunities within peptide ADME (absorption, distribution, metabolism and elimination) were presented and discussed at the 3rd online workshop of the Peptide ADME Discussion Group (3rd of February 2021). This article summarises the presentations and discussions from this workshop.The following topics were covered:Peptide drug-drug interactionsImpact of septic shock on PK and PD of the peptide selepressinMS processing software for metabolite identification of peptidesProfiling of peptides in preclinical drug developmentStrategy for immunogenicity testing of peptides stability testing of peptides for inhalation and automated LC-MS.

Meeting report: 2nd workshop of the peptide ADME discussion group.

Challenges and opportunities within peptide ADME (absorption, distribution, metabolism and elimination) were presented and discussed at the 2nd workshop of the Peptide ADME Discussion Group in Cambridge, UK (17th of September 2019). This article summarises the presentations and discussions from this workshop. The following topics were covered: Peptide drug-drug interactions (DDIs) Regulatory perspectives on peptide ADME studies Bioavailability of therapeutic peptides impacted by metabolism and oligomerization in the subcutaneous compartment Regulated bioanalysis of parent peptide and active metabolites by immunoaffinity LC-MS/MS Peptide radiopharmaceutical development.

Meeting report: 1st workshop of the peptide ADME discussion group.

1. Challenges and opportunities within peptide ADME (absorption, distribution, metabolism and elimination) were presented and discussed at the 1st peptide workshop of the Peptide ADME Discussion Group in Gothenburg, Sweden (15th of October 2018). This article summarises the presentations and discussions from this 1st workshop.

Pharmacokinetics, tissue distribution, excretion, and metabolite profiling of PEGylated rFIX (nonacog beta pegol, N9-GP) in rats.

Nonacog beta pegol (N9-GP) is a novel recombinant factor IX conjugated with a 40-kDa branched polyethylene glycol (PEG) to extend plasma half-life (t½) compared with native FIX, developed for the treatment of haemophilia B. This is the first time distribution, metabolism, and excretion data of N9-GP have been presented. ADME studies were performed using single i.