Evolving Approaches on Measurements and Applications of Intracellular Free Drug Concentration and Kpuu in Drug Discovery

Date: September 26 2023
Presenter(s): Li Di, PhD

Timing: 8 am (PST), 11 am (EST), 4 pm (GMT), 5 pm (CET)

Summary of the Presentation:

Intracellular-free drug concentration (Cu,cell) and unbound partition coefficient (Kpuu) are two important parameters to develop pharmacokinetic and pharmacodynamic relationships, predict drug-drug interaction potentials and estimate therapeutic indices.  Methods on measurements of Cu,cell, Kpuu, partition coefficient (Kp) and fraction unbound of cells (fuc) will be discussed including the advantages and limitations of the different approaches.  Cu,cell and Kpuu of cells and tissues are commonly applied to: (1) Bridging the potency gaps between biochemical and cell-based assays; (2) Predicting tissue Kpuu for development of PK/PD relationships; (3) Addressing enzyme and transporter interplay in prediction of clearance and drug-drug interactions; and (4) Developing structure-Kpuu relationships to guide structure modifications in order to enrich or restrict tissue distribution. Applications of Cu,cell and Kpuu are growing and expanding in drug discovery. Methods for measurements of these properties continue to evolve in order to achieve higher precision/accuracy and obtain more detailed information at the subcellular organelle levels. Future directions of the field include the development of in vitro and in silico models to predict tissue, cell and organelle Kpuu, direct measurement of free drug concentration in subcellular organelles, and further investigations into the critical elements governing cell and tissue Kpuu. Significant innovation is needed to advance this complex, but highly impactful and exciting area of science.

About the presenter:

DI Li, PhD

Research Fellow, Pfizer Worldwide Research and Development, Groton, CT


Dr. Li Di has 30 years of experience in the pharmaceutical indus­try including Pfizer, Wyeth and Syntex. She is currently a research fellow at Pfizer Worldwide Research and Development, Groton, CT. Her research interests include the areas of drug metabo­lism, pharmacokinetics, drug-drug interactions, absorption, transporters, blood–brain barrier and PBPK modeling and simulation. She has over 180 publications including two books and presented over 100 invited lectures. She is a recipient of the Thomas Alva Edison Patent Award, the New Jersey Association for Biomedical Research Outstanding Woman in Science Award, the Wyeth President’s Award and Peer Award for Excellence.