Title:Pharmacokinetics/Pharmacodynamics Model-Supported Early Drug Development
VOLUME: 13 ISSUE: 7
Author(s):Bin Chen, Jennifer Q. Dong, Wei-Jian Pan and Ana Ruiz
Affiliation:Global Clinical Pharmacology, Johnson & Johnson Pharmaceutical Research & Development.
Keywords:Biopharmaceutical, drug discovery, early drug development, modeling & simulation, pharmacokinetics/ pharmacodynamics.
Abstract:Pharmacokinetic/pharmacodynamic (PK/PD) modeling & simulation (M&S) provides quantitative assessment
of dose/exposure-response relationships with extensive applications at the late stage drug development as well as during
regulatory decision making. However, at preclinical and early phase clinical drug development, the importance of PK/PD
M&S has not been as widely recognized. We reviewed selected PK/PD M&S literatures in order to convey importance of
M&S in these early development phases. We focused on the application of M&S to select and optimize lead candidates,
the use of preclinical PK/PD data to project the range of clinical doses, and the development of comprehensive
dose/exposure-response models that can be used to forecast the probability of achieving a target response based on Phase
1 safety, PK and biomarker information. We also reviewed several other M&S approaches that are often used in early
drug development such as physiologically-based pharmacokinetic (PBPK) modeling, meta-analysis, PK-pharmacogenomics
modeling, and etc. Our aims were to provide expert opinions on the practical utility of PK/PD model-based approaches
that have positive impact on early decision-making with the goal of improving the success rate of early to late stage drug
development.
