Absorption Models Based on Structure

A rapid popular screen for compounds likely to be poorly absorbed is Lipin-ski s [218] rule of 5, which states that poor absorption of a compound is more likely when its structure is characterized by  

However, compounds that are substrates for biological transporters are exceptions to the rule. Based on the analysis of 2, 200 compounds in the World Drug Index that survived Phase I testing and were scheduled for Phase II evaluation, Lipinski s rule of 5 revealed that less than 10% of the compounds showed a combination of any two of the four parameters outside the desirable range. Accordingly, the rule of 5 is currently implemented in the form if two parameters are out of range, a poor absorption is possible. However, compounds that pass this test do not necessarily show acceptable absorption. 

Although various computational approaches for the prediction of intestinal drug permeability and solubility have been reported [219], recent computer-based absorption models utilize a large number of topological, electronic, and geometric descriptors in an effort to take both aqueous drug solubility and permeability into account. Thus, descriptors of partitioned total surface areas [168], Abraham molecular descriptors [220,221], and a variety of structural descriptors in combination with neural networks [222] have been shown to be determinants of oral drug absorption. 

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