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High-throughput Determination of the Free Fraction of Drugs Strongly Bound to Plasma Proteins by Joachim Schuhmacher; Christian Kohlsdorfer; Klaus Bühner; Tim Brandenburger; Renate Kruk is a Chemistry article available to read on EtoBox.

What is High-throughput Determination of the Free Fraction of Drugs Strongly Bound to Plasma Proteins about?

Quantification of protein binding of new chemical entities is an important early screening step during drug discovery and is of fundamental interest for the estimation of safety margins during drug development. In this publication, we describe the development of a new high-throughput assay for the determination of the free drug fraction in plasma (f u ). The new technique is an enhancement of the previously published erythrocytes partition method. It is based on the distribution of drugs between plasma water, plasma proteins, and solid-supported lipid membranes (Transil 1 ). The execution of protein binding studies by partitioning is dramatically simplified by substituting erythrocytes with commercially available Transil 1 beads, and makes the method particularly suitable for high-throughput studies. Eight Bayer compounds from different compound classes covering a wide range of lipophilicities (log P 1⁄4 1.9-5.6) and f u values (0.018-35%) were selected for validation of the assay. The results obtained by the new method and by either the erythrocytes partitioning technique or more conventional methods (ultrafiltration and equilibrium dialysis) are identical, confirming that the new

Who reads High-throughput Determination of the Free Fraction of Drugs Strongly Bound to Plasma Proteins?

Author

Joachim Schuhmacher; Christian Kohlsdorfer; Klaus Bühner; Tim Brandenburger; Renate Kruk

Publisher

John Wiley and Sons; Elsevier ; Elsevier Inc.; Elsevier BV (ISSN 0022-3549)

Published

2004

Language

EN

Field

Chemistry (Physical Sciences)