Hydrophobicity and Absorption

From data on human intestinal absorption of drug molecules (excluding compounds having absorptions either 0 or 100%), the following model was developed by Abraham et al  

This analysis raises a question. Does a comparison between the log k and log Poet equations justify a conclusion that log Poet is not a suitable predictor for human intestinal absorption Although both log k and log Poet constitute the identical dependent variables for equations (7.17) and (7.15), respectively, log k represents a biological activity while log Poet is a physicochemical property. In order to clarify this confusion, we developed the following QSAR (7.18), based on the same data used by Abraham et al  

Outliers ouabain, acarbose, lincomycin, sorivudine, lamivudine and amrinone. 

Two compounds are not considered in the analysis due to their name/ structure confusion. This is a parabolic correlation in terms of dog P with well-defined optimum dog P of 2.52 and suggests that log Poet is a suitable predictor for the human intestinal absorption in a parabolic fashion. It has been shown that compounds with log P values between zero and three are ideal for passive transcellular absorption across intestinal epithelia.  

Data on the inhibition of demethylation of aminopyrine in microsomes from Phenobarbital-treated rat liver CYP by 4-X-phenoxyanilines, resulted in the delineation of QSAR 7.20. 

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By introducing fluorine atoms to the polyenic system of retinal, the geometry, electronic properties, hydrophobicity, and absorption properties of the molecule will be modified. Thus, fluoro derivatives of retinal are useful tools to understand the interactions between retinal and opsin, especially on the level of charge and hydrophobic effects at the protein site. Moreover, fluorine atoms are probes in NMR and allow studies on model molecules of visual pigments Consequently, syntheses of mono-, di-, and trifluoro derivatives of retinal have been the subject of many investigations. 

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