Physicochemical properties of drug candidates

Kibbey, C. E., Poole, S. K., Robinson, B., lackson,. D., Durham, D. An integrated process for measuring the physicochemical properties of drug candidates in a preclinical discovery environment. J. Pharm. Sci. 2001, 90, 1164-1175. 

Kerns EH (2001) High Throughput Physicochemical Profiling for Drug Discovery. J Pharm Sci 90(11) 1838-1858 Kibbey CE, Poole SK, Robinson B et al. (2001) An Integrated Process for Measuring The Physicochemical Properties of Drug Candidates in a Preclinical Discovery Environment. J Pharm Sci 90(8) 1164-1175... 

PK parameters can be characterized as descriptive or mechanistic parameters. The descriptive parameters are those used to describe exposure, while the mechanistic ones are the intrinsic properties of compounds controlling the extent and duration of exposure. Understanding the true meaning and relationship between these two categories is important for improving the chemical and physicochemical properties of drug candidates. 

The dosage-form design is guided by the properties of the drug candidate. If an NCE does not have suitable physical and chemical properties or pharmacokinetic attributes, the development of a dosage form (product) may be difficult and may sometimes be even impossible. Any heroic measures to resolve issues related to physicochemical and biopharmaceutical properties of drug candidates add to the time and cost of drug... 

Model systems needed for particular studies are listed in Figure 5.2. In addition, in silico models are developed to predict drug behaviors based on physicochemical properties of drugs or drug candidates, crystal structures of a protein (an enzyme or a transporter), and database of ADME properties generated in laboratories. Therefore, experimental models are important for ADME studies. The objective of this chapter is to discuss strategy and applications of experimental models in drug metabolism and disposition. 

The parallel screening of drug candidates for their pharmacological activity and for their physicochemical and biopharmaceutical properties has become a major challenge in dmg development and is performed at very early stages... 

Among physicochemical properties, the stability of drug candidates is receiving increasing attention. Unfortunately, its evaluation very often requires a lot of experimental time and profiling of many molecules would be nearly impossible without new, computer-aided methods. Any effort useful to facilitate this first part of pharmaceutical investigation is appreciated because it can be converted to a considerable lowering of the research cost. 

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