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The consequences of metabolic transformation on lipophilicity have been considered using the terms log P (partition coefficient) and log D (distribution coefficient). 2. Transformations which result in no change in the degree of ionisation can be readily predicted by the use of fragmental constants and log P. 3. If metabolism alters the degree of ionization then the distribution coefficient, log D, at physiological pH is a more appropriate term to use. Intuitive empirical observations may be incorrect and lead to false assumptions about the lipophilicity or water solubility of metabolites. 4. Metabolism may form zwitterionic molecules. These metabolites need special consideration since their penetration into lipid phases may be greater than expected.
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Manners et al. (1988) studied this question.
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