Partition Coefficient - Limitations

Limitations

Log P is not an accurate determinant of lipophilicity for ionizable compounds because it only correctly describes the partition coefficient of neutral (uncharged) molecules. Taking the example of drug discovery we see how the limitations of log P can affect research. Since the majority of drugs (approximately 80%) are ionizable, log P is not an appropriate predictor of a compound's behaviour in the changing pH environments of the body. The distribution coefficient (Log D) is the correct descriptor for ionizable systems. Alternatively, use may be made of the apparent partition coefficient, which is defined as follows: (true partition coefficient) x (fraction of the drug that is unionised). Clearly, if the drug is 100% unionised then Papparent = Ptrue.

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