Drug discovery phase

The main input parameter used to define the highest possible drug concentration in the intestine and to calculate the dissolution rate in the GI tract is the solubility of the dmg in the GI fluids. As described earlier (Sect. 21.2) there are several, both physiological and physicochemical, factors that can affect the solubility in the GI tract and it is therefore important to consider the relevance of the solubility data generated in the early drug discovery phase. A common approach is to use in silico models to predict the solubility of drugs (e.g., [5]). The advantage of this approach is that only the chemical... 

Table 4.1 Major components of drug discovery phase and their challenges. Included from [4] with permission from Wiley Periodicals.

Figure 13.3 (a) Plot of selectivity score versus promiscuity score applied to MDDR. Red dots are marketed drugs. Marketed drugs clearly cluster when compared to other compounds in different drug discovery phases (green dots), (b) The predicted selectivity of compounds in different phases of the drug discovery process. 

There are several natural milestones during drug development, and although there are differences between companies, both in the number and in the names of the milestones, these differences are quite small. The first milestone is the selection of a compound in the drug discovery phase for development. In the past this decision was exclusively based on the pharmacology (potency, selectivity) of the compound. Since there is now greater awareness that compounds with attractive pharmacological properties may fail later because of poor solubility or extensive metabolism, the physical chemistry, preliminary PK and metabolism characteristics of the... 

For the use of these models in the drug discovery phase, one can identify two scenarios ... 

Chen Y, Jin JY, Mukadam S, Malhi V, Kenny JR. 2012. Application of IVIVE and PBPK modeling in prospective prediction of clinical pharmacokinetics strategy and approach during the drug discovery phase with four case studies. Biopharm Drug Dispos 33 85-98. 

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