Penetrant molecules transport properties, absorption

The Admensa Interactive tool developed by scientists from Inpharmatica incorporates several ADME properties, namely log P, log Dy 4 (log P at pH 7.4), aqueous solubility, human intestinal absorption, BBB penetration, cytochrome P450 (CYP) affinities, P-glycoprotein transport, hERG inhibition and PPB to score and prioritize their molecules. 

Generally, compounds with log P values between one and three show good absorption, whereas those with log Ps greater than six or less than three often have poor transport characteristics. Highly nonpolar molecules have a preference to reside in the lipophilic regions of membranes, and highly polar compotmds show poor bioavailabiUty because of their inability to penetrate membrane barriers. Thus, there is a parabolic relationship between log P and transport, that is, candidate drugs that exhibit a balance between these two properties will probably show the best oral bioavailability. 

Occupational disease, caused by skin contact with toxic substances, represents a major health problem In the United States (1). Dermal exposure of agricultural workers to pesticide agents, of course. Is a particularly pertinent example of this problem. Prediction of the detrimental toxic effects of hazardous chemical exposure Is difficult, however, because of the complexity of the percutaneous absorption process in man and a lack of any consistently Identifiable relatlonshlp(s) between transport rate and chemical properties. In addition, the very diverse approaches, which have been used to measure skin penetration, further complicate the situation since the extrapolation of results to man In his workplace may Involve questionable, non-valldated assumptions. Our specific aim Is to predict accurately the toxicokinetics of occupationally-encountered molecules (e.g., pesticides) absorbed across human skin In vivo. We present... 

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