Skip to main page content
Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2016;8(2):229-45.
doi: 10.1080/19420862.2015.1115937. Epub 2015 Dec 4.

Key Factors Influencing ADME Properties of Therapeutic Proteins: A Need for ADME Characterization in Drug Discovery and Development

Affiliations
Free PMC article
Review

Key Factors Influencing ADME Properties of Therapeutic Proteins: A Need for ADME Characterization in Drug Discovery and Development

Jay Tibbitts et al. MAbs. .
Free PMC article

Abstract

Protein therapeutics represent a diverse array of biologics including antibodies, fusion proteins, and therapeutic replacement enzymes. Since their inception, they have revolutionized the treatment of a wide range of diseases including respiratory, vascular, autoimmune, inflammatory, infectious, and neurodegenerative diseases, as well as cancer. While in vivo pharmacokinetic, pharmacodynamic, and efficacy studies are routinely carried out for protein therapeutics, studies that identify key factors governing their absorption, distribution, metabolism, and excretion (ADME) properties have not been fully investigated. Thorough characterization and in-depth study of their ADME properties are critical in order to support drug discovery and development processes for the production of safer and more effective biotherapeutics. In this review, we discuss the main factors affecting the ADME characteristics of these large macromolecular therapies. We also give an overview of the current tools, technologies, and approaches available to investigate key factors that influence the ADME of recombinant biotherapeutic drugs, and demonstrate how ADME studies will facilitate their future development.

Keywords: Absorption; antibody-drug conjugate (ADC); biologics; biotherapeutics; distribution; excretion; imaging; labeling; metabolism; monoclonal antibody (mAb); neonatal Fc receptor (FcRn); pharmacokinetics; subcutaneous bioavailability.

Similar articles

See all similar articles

Cited by 15 articles

See all "Cited by" articles

References

    1. Lewis P. Recombinant Protein drugs. Br J Cin Pharmacol 2002; 53: 411; http://dx.doi.org/10.1046/j.1365-2125.2002.01571.x - DOI
    1. Reichert JM. Marketed therapeutic antibodies compendium. MAbs 2012; 4: 413-15; PMID:22531442; http://dx.doi.org/10.4161/mabs.19931 - DOI - PMC - PubMed
    1. Berggren R, Moller M, Moss R, Poda P, Smietana K. Outlook for the next 5 years in drug innovation. Nat Rev Drug Discov 2012; 11: 435-36; PMID:22653208; http://dx.doi.org/10.1038/nrd3744 - DOI - PubMed
    1. Morgan P, Van Der Graaf PH, Arrowsmith J, Feltner DE, Drummond KS, Wegner CD, Street SD. Can the flow of medicines be improved? Fundamental pharmacokinetic and pharmacological principles toward improving Phase II survival. Drug Discov Today 2012; 17: 419-24; PMID:22227532; http://dx.doi.org/10.1016/j.drudis.2011.12.020 - DOI - PubMed
    1. European Medicines Agency Guideline on the clinical investigation of the pharmacokinetics of therapeutic proteins. 2007.

Substances

LinkOut - more resources

Feedback