Investigating Intracellular Free Drug Partitioning (Kpuu)

Webinar on the Evolving Applications of Intracellular Free Drug Concentration and Kp_uu in Drug Discovery

Intracellular-free drug concentration (C_u,cell) and unbound partition coefficient (Kp_uu) are two important parameters to develop pharmacokinetic and pharmacodynamic relationships, predict drug-drug interaction potentials, and estimate therapeutic indices.

Methods for measuring C_u,cell, Kp_uu, partition coefficient (Kp), and fraction unbound of cells (f_u,c) are discussed in detail, including the advantages and limitations of the different approaches. C_u,cell and Kp_uu of cells and tissues are commonly applied to:

• Bridging the potency gaps between biochemical and cell-based assays
• Predicting tissue Kp_uu for development of PK/PD relationships
• Addressing enzyme and transporter interplay in prediction of clearance and drug-drug interactions
• Developing structure-Kp_uu relationships to guide structure modifications in order to enrich or restrict tissue distribution

Applications of C_u,cell and Kp_uu 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 Kp_uu, direct measurement of free drug concentration in subcellular organelles, and further investigations into the critical elements governing cell and tissue Kp_uu. Significant innovation is needed to advance this complex but highly impactful and exciting area of science.

Consult an expert

Webinar Presenter

Li Di, PhD
Research Fellow
Pfizer Worldwide Research and Development, Groton, CT