Application of biomimetic HPLC to estimate in vivo behavior of early drug discovery compounds

Abstract

Characterizing the properties of large numbers of compounds and estimating their potential absorption, distribution, metabolism and elimination properties are important early stages in the process of drug discovery and help to reduce later stage attrition. The chromatographic separation principles using stationary phases that contain proteins and phospholipids are more suitable for compound characterization and estimation of the pharmacokinetic properties than the traditional octanol/water partition coefficient. This technology, when standardized, enables the prediction of in vivo behavior and the selection of compounds with the best potential, thus reducing the number of animal experiments. Chromatography may be involved more widely in the future to measure kinetic aspects of compounds’ binding to proteins and receptors which would enable designing compounds that require a lower frequency of doses and have more predictable pharmacokinetic profiles.

Lay abstract

The measurement of the molecular properties of potential drug molecules is now an established component of modern drug design strategies. Chromatographic separation now plays an essential role in this process in the estimation of pharmacokinetic properties and may be extended in the future to protein and receptor binding kinetics. These strategies will also offer cost savings and reduce the need for animal experiments.