Pharmacokinetics and Pharmacodynamics of Therapeutic Peptides and Proteins

  • Bernd MeibohmEmail author


The rational use of drugs and the design of effective dosage regimens are facilitated by the appreciation of the central paradigm of clinical pharmacology that there is a defined relationship between the administered dose of a drug, the resulting drug concentrations in various body fluids and tissues, and the intensity of pharmacologic effects caused by these concentrations. This dose-exposure-response relationship and thus the dose of a drug required to achieve a certain effect are determined by the drug’s pharmacokinetic and pharmacodynamic properties. The understanding of the dose-concentration-effect relationship is crucial to any drug—including peptides and proteins—as it lays the foundation for dosing regimen design and rational clinical application. General pharmacokinetic and pharmacodynamic principles are to a large extent equally applicable to protein and peptide drugs as they are to traditional small molecule-based therapeutics. Deviations from some of these principles and additional challenges with regard to the characterization of the pharmacokinetics and pharmacodynamics of therapeutic peptides and proteins, however, arise from some of their specific properties. This chapter will highlight some of the major pharmacokinetic properties and processes relevant for the majority of therapeutic peptides and proteins and will provide examples of well-characterized pharmacodynamic relationships for protein drugs.


Pharmacokinetics Pharmacodynamics Therapeutic proteins Monoclonal antibodies Immunogenicity PKPD-modeling Pharmacometrics Drug development 


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Further Reading

    General Pharmacokinetics and Pharmacodynamics

    1. Atkinson A, Abernethy D, Daniels C, Dedrick R, Markey S (2006) Principles of clinical pharmacology. Academic, San DiegoGoogle Scholar
    2. Bonate PL (2011) Pharmacokinetic-pharmacodynamic modeling and simulation. Springer, New YorkCrossRefGoogle Scholar
    3. Derendorf H, Meibohm B (1999) Modeling of pharmacokinetic/pharmacodynamic (PK/PD) relationships: concepts and perspectives. Pharm Res 16(2):176–185PubMedCrossRefGoogle Scholar
    4. Gabrielsson J, Hjorth S (2012) Quantitative pharmacology. Swedish Academy of Pharmaceutical Sciences, StockholmGoogle Scholar
    5. Gibaldi M, Perrier D (1982) Pharmacokinetics. Marcel Dekker, New YorkGoogle Scholar
    6. Holford NH, Sheiner LB (1982) Kinetics of pharmacologic response. Pharmacol Ther 16(2):143–166PubMedCrossRefGoogle Scholar
    7. Rowland M, Tozer TN (2011) Clinical pharmacokinetics and pharmacodynamics: concepts and applications. Lippincott Williams & Wilkins, BaltimoreGoogle Scholar

    Pharmacokinetics and Pharmacodynamics of Peptides and Proteins

    1. Diao L, Meibohm B (2013) Pharmacokinetics and pharmacokinetic-pharmacodynamic correlations of therapeutic peptides. Clin Pharmacokinet 52(10):855–868PubMedCrossRefGoogle Scholar
    2. Diao L, Meibohm B (2015) Tools for predicting the PK/PD of therapeutic proteins. Expert Opin Drug Metab Toxicol 11(7):1115–1125PubMedCrossRefGoogle Scholar
    3. Kontermann R (2012) Therapeutic proteins: strategies to modulate their plasma half-lives. Wiley, WeinheimCrossRefGoogle Scholar
    4. Meibohm B (2006) Pharmacokinetics and pharmacodynamics of biotech drugs. Wiley, WeinheimCrossRefGoogle Scholar
    5. Mould DR, Meibohm B (2016) Drug development of therapeutic monoclonal antibodies. BioDrugs 30(4):275–293PubMedCrossRefGoogle Scholar
    6. Ryman JT, Meibohm B (2017) Pharmacokinetics of monoclonal antibodies. CPT: Pharmacometrics Syst Pharmacol 6(9):576–588Google Scholar
    7. Tang L, Persky AM, Hochhaus G, Meibohm B (2004) Pharmacokinetic aspects of biotechnology products. J Pharm Sci 93(9):2184–2204PubMedCrossRefGoogle Scholar

Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  1. 1.Department of Pharmaceutical SciencesUniversity of Tennessee Health Science Center, College of PharmacyMemphisUSA

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