Apparent partition coefficients, Papp

Papp is the apparent partition coefficient that varies with pH. Thus it can be seen when a compound, acid or base, is 50% ionised (i.e. pH = pA a) its partition coefficient is half that of the drug in the un-ionised state ... 

Ptrue is a constant for a given drug and allows comparison of P values for different molecules. The apparent partition coefficient is the partition coefficient measured in the laboratory. If the drug in question ionises, Papp will vary with the pH of measurement. 

The dissociation equilibrium depends on the pH value of the aqueous phase and on the pA a value of the organic compound. Equation (34) (for acids) and Eq. (35) (for bases) describe the apparent partition coefficients log Papp of acids and bases at different pH values of the aqueous phase in an -octanol/buffer system ( Pu = partition coefficient of the neutral, uncharged form P = partition coefficient of the ionized,... 

Equations (34) and (35) describe sigmoidal curves with apparent partition coefficients log Papp = log Pu at pH < pATa (acids) and pH > pK (bases), and apparent partition coefficients log Papp - log P at pH3>pATa (acids) and pHwith constant Papp values for the neutral forms and steadily decreasing Papp values with increasing ionization, at pH > pKa for acids and pH < pATa for bases. 

Papp is the apparent partition coefficient, which varies with pH, because it is taking account of the distribution of the drug. Remember, P is a constant because it refers to the partition coefficient of only the un-ionised form. 

The validity of the approach based on (6.2) was proven when the fraction of dose absorbed, Fa, was found to increase with AP for several drugs with a wide variety of physicochemical properties and various degrees of extent of absorption [156]. Additional support for the AP concept was provided by a 3-dimensional plot of Fa as a function of the ionization-solubility/dose term (fun/9) and the octanol/water partition coefficient Pc [157]. In fact, because of the recent interest in the apparent permeability estimates Papp measured in the in vitro Caco-2 monolayer system, it was suggested that Papp can replace the octanol/water partition coefficient Pc in (6.2) [157]. 

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