ADMET and DMPK

Special issue: Chromatographic techniques to support ADMET&DMPK in early drug discovery

Guest Editor: Klara Valko


The drug discovery process usually starts with discovering a potent new chemical identity that showed some activity on a target that is believed to be relevant in a certain type of disease. However, the structure and property of these putative drug molecules have to be modified in order to ensure they are able to exert the desired in vivo pharmacological effect. The molecules have to be absorbed from the gastrointestinal system showing appropriate solubility and permeability and then reaching the target enzyme in vivo with a sufficient free biophase concentration at the site of action. The dosing regimen has to be appropriate for the patients thus the distribution and elimination properties have to be optimized as well. The ADME studies usually require animal experiments or the use biological samples, tissues which is expensive and time-consuming. New technologies and approaches can accelerate this process.


HPLC methodology is well established and used throughout the drug discovery process for analytical measurements of the compound’s purity and concentration in various biological samples such as blood, plasma, tissues etc. During the HPLC separation process, the compounds distribute between the mobile and the stationary phases. As different compounds have a different interaction with the stationary phase that is modified by the mobile phase they move at a different speed through the chromatographic system resulting in different retention times. As these retention times are characteristic of the compound and the HPLC system and can be related to compound’s dynamic distribution coefficients they can be used to describe the properties of the compounds. When biomimetic stationary phases are used during chromatography, such as albumin, glycoprotein, and phospholipids, the calibrated retention times can be converted to binding constants to these body components. Then these data can be used to estimate the compound’s in vivo distribution behavior.


Several efforts have also been published to alter the chromatographic systems to become a better model of in vivo distribution. Thus, micellar bio partitioning chromatography has been developed. Using the Abraham solvation equations that describe the relationships between solute properties and the molecular descriptors the coefficients can be used to search for surrogate chromatographic systems that model a particular biological process. In this special issue, we would like to invite contributors working in this field to present their later results or review the efforts and achievements of the application of chromatographic techniques to support drug discovery.


Beside original scientific papers, reviews, opinions or commentary articles are welcome.

 

The deadline for article submission is March 01, 2018. 



ISSN 1848-7718