Lipophilicity and absorption

The parabolic nature of activity-log P plots is due to a combination of factors with dmgs with high log P values, protein binding, low solubility and binding to extraneous sites cause a lower measured activity than if it were 

System Solute or drug Log (octanol/water) for maximal transport 

Buccal cavity (human) Bases 5.52 (undissociated) 3.52 (dissociated) 

The larger drug molecules are, the poorer will be their ability to traverse biological membranes. The change of permeability with increasing molecular size is shown in Fig. 9.4. 

In a survey of over 2000 dmgs only 11% had molecular weights above 500, and only 8% had molecular weights above 600. Lipinski devised the so-called Rule of 5 which refers to drug-like properties of molecules. It states that poor oral absorption is more likely when the drug molecule  

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