Logarithmic distribution coefficient

A general definition of log P and log D, in its simplest form, can be given as the logarithm of the ratio (P or D) of the concentration of species of interest (the drug in a pharmaceutical context) in each phase, assuming the phases are immiscible and well separated prior to analysis. P is defined as the partition coefficient, whereas D is the distribution coefficient. However, the simplest form does not reveal some of the intricacies of the determination and use of these parameters, and further explanation is necessary. 

Another perspective provided by this model is the effect of three physiochemical parameters—solubility, distribution coefficient, and molecular mass—on transcoreal flux. All of these properties can be influenced by molecular design. The effects of these properties are illustrated in Fig. 13, in which the logarithm of the flux is plotted as a function of solubility and distribution coefficient for two different Mr. Several features of the model are depicted, and these qualitative, or semi-quantitative, aspects presumably encompass the principles of corneal permeation. 

A log P Difference between log P in octanol/water and alkane/water log D Logarithm of the distribution coefficient in octanol/water at pH 7.4 log P Logarithm of the partition coefficient in octanol/water (for neutral species)... 

Logarithm of the distribution coefficient in octanol/water at pH 6.5 Molecular weight... 

Polarity term, mainly related to hydrogen bonding capability of a solute Logarithm of the partition coefficient (P) of neutral species Logarithm of the distribution coefficient (D) at a selected pH, usually assumed to be measured in octanol/water... 

Logarithm ofthe distribution coefficient (D) at a selected pH, measured in octanol/water... 

Eq. 2 pKt, inhibition constant Mr, relative molecular mass, log D1A, logarithm of the distribution coefficient at pH 7.4 HBA, number of hydrogen bond acceptors. 

For example, the ratio of the n-octanol/watcr distribution coefficient of the nondissociated species to that of the ionic species is nearly 10,000 for 3-methyl-2-nitrophenol, but only about 1000 for pentachlorophenol because of the greater significance of the hydrophobicity of the ionized form of pentachlorophenol. The logarithm of the -octanol/water distribution coefficient of pentachlorophenol as the phenolate is about 2 (determined at pH 12, and 0.1 M KC1), which indicates significant distribution of the ionized form into the n-octanol phase [8,37], Extraction of such highly hydrophobic ionogenic organic compounds can result from mixed-mode mechanisms that incorporate both the hydrophobic and ionic character of the compound. 

The partition coefficient itself is a constant and is defined as the ratio of concentration of compound in aqueous phase to the concentration in an immiscible solvent, as the neutral molecule. In practical terms the neutral molecule exists for bases >2 pH units above )Ka and for acids >2 pH units below pKa. In practice, log P will vary according to the conditions under which it is measured and the choice of partitioning solvent. LogP is the logarithm of distribution coefficient at a pH where analyte is in its neutral state. This is not a constant and will vary according to the protogenic nature of the molecule. 

Partition coefficient discussed above represents oil/water equilibrium distribution of only neutral forms of a substance. The distribution at different pH is described by LogD, which is the logarithm of the ratio of the concentrations of all forms of analyte in oil and water phases at particular pH. Logarithm of distribution coefficient at pH 7.4 is often used to estimate the lipophUicity of a drug at the pH of blood plasma. 

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