Tools for predicting the PK/PD of therapeutic proteins.
BACKGROUND
Assessments of the pharmacokinetic/pharmacodynamic (PK/PD) characteristics are an integral part in the development of novel therapeutic agents. Compared with traditional small molecule drugs, therapeutic proteins possess many distinct PK/PD features that necessitate the application of modified or separate approaches for assessing their PK/PD relationships.


METHODS
In this review, the authors discuss tools that are utilized to describe and predict the PK/PD features of therapeutic proteins and that are valuable additions in the armamentarium of drug development approaches to facilitate and accelerate their successful preclinical and clinical development.


CONCLUSIONS
A variety of state-of-the-art PK/PD tools is currently being applied and has been adjusted to support the development of proteins as therapeutics, including allometric scaling approaches, target-mediated disposition models, first-in-man dose calculations, physiologically based PK models and empirical and semi-mechanistic PK/PD modeling. With the advent of the next generation of biologics including bioengineered antibody constructs being developed, these tools will need to be further refined and adapted to ensure their applicability and successful facilitation of the drug development process for these novel scaffolds.
Biogen Idec, Clinical Pharmacology and Pharmacometrics , Cambridge, MA , USA.
Lei
L
Diao
Bernd
B
Meibohm
D000818:Animals; D004305:Dose-Response Relationship, Drug; D015195:Drug Design; D004353:Drug Evaluation, Preclinical / Q000379:methods; D006801:Humans; D008954:Models, Biological; D011506:Proteins / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000494:pharmacology
D011506:Proteins
MABEL; PBPK-modeling; PK/PD modeling; allometric scaling; pharmacodynamics; pharmacokinetics; therapeutic proteins