Drug development species differences

The extrapolation of animal data to predict pharmacokinetic parameters by allo-metric scaling is an often-used tool in drug development, with multiple approaches available at variable success rates [99-101]. In the most frequently used approach, pharmacokinetic parameters between different species are related via body weight using a power function ... 

In vitro cell-based models have been developed to aid in the evaluation of ADMET properties of compounds to explore the influences of species differences. CaCo-2 cells, for example, constitute an immortalized line of heterogeneous human epithelial colorectal adenocarcinoma cells widely used to predict the absorption rates of candidate drug compounds across the intestinal epithelial cell barrier. Drug absorption rates are determined 21 days after CaCo-2 cell seeding to allow for monolayer formation and cell differentiation. 

Polymorphism is an ability of the drug substance to form crystals with different molecular arrangements giving distinct crystal species with different physical properties such as solubility, hygroscopicity, compressibility, and others. This phenomenon is well known within pharmaceutical companies. The reader can find additional information in references 47 and 48. The determination of possible polymorphic transition and existence of thermodynamically unstable forms during preformulation stage of drug development is important. Typical methods used for solid-state characterization of polymorphism are DSC,... 

The enormous diversity of microorganisms is a factor that must be kept in mind for future drug development. Only a minor proportion of bacteria and fungi have been cultured or examined for secondary metabolite production. For example, only 5% of the total number of fungal species have been described. Of those described (69,000), only 16% (11,500) have been cultured. It has been estimated that 1 gram of soil contains 1000 to 10,000 species of undiscovered prokaryotes The extensively used concept of isolation of microbial strains fixim different geographical and climatic locations around the world still gathers support. ... 

Should an early decision be made to develop the eutomer, then the drug development program would be the same as for conventional NCEs, with the possible exception that assessment of in vitro and/or in vivo chiral inversion may be desirable. However, if development continues with the racemate, time, cost, and staff resource commitments become magnified. For example, a very important variable to consider is spedes differences in enantiomer exposure. Appropriate toxicokinetic studies are advisable in order to assure that, at toxicological doses, the animal species tested have attained suffident plasma concentrations of each enantiomer to support clinical evaluation at therapeutic doses in humans. The enantiomeric ratio (based on maximum drug concentrations fCmax] and/or area under the plasma drug concentration-time curve [ALJC]) should be evaluated, and... 

---