Partition and Distribution Coefficients

Hence, two drugs of similar ogP may differ greatly in logZ) at physiological pH, with profound consequences for their pharmacological activity. As a consequence, log/ values of ionizable compounds are often quoted at pH 7.4, and equations similar to those above are used in pH-metric techniques [117-124] to determine either log/ or logZ). A compilation of the principal relationships linking partition and distribution coefficients is available in Refs. 125 and 126. 

Chmelfk, J. Hudecek, J. Putyera, K. Makovicka, J. Kalous, V. Chmelikova, J., Characterization of the hydrophobic properties of amino acids on the basis of their partition and distribution coefficients in the 1-octanol-water system, Collect. Czech. Chem. Commum. 56, 2030-2040 (1991). 

Clarke, F. H. Cahoon, N. M., Ionization constants by curve fitting Determination of partition and distribution coefficients of acids and bases and their ions, J. Pharm. Sci. 76, 611-620 (1987). 

Alcorn, C. J. Simpson, R. J. Leahy, D. E. Peters, T. J., Partition and distribution coefficients of solutes and drugs in Brush Border membrane vesicles, Biochem. Pharmacol. 45, 1775-1782 (1993). 

The partition coefficient (log P) describes the intrinsic lipophilicitY of the collection of functional groups and carbon skeleton, which combine to make up the structure of the compound, in the absence of dissociation or ionization. Methods to measure partition and distribution coefficients have been described [3,4]. 

Various aspects of structure activity relationships in 4,5-epoxymorphinans have been reviewed,(201,46 U467) and specific consideration has been given to quantum chemical studies with particular reference to polar group variation,(468) stereoisomeric ligands as receptor probes, 469 partition and distribution coefficients, 470 471 and antagonists. 145 ... 

These are only the theoretical dependencies real behavior of actual molecule usually is significantly altered due to different types of intermolecular interactions. Molecular solvation, association, hydrogen bonding, and counterions all have a significant effect on drug ionization constant and partitioning and distribution coefficients. Detailed and comprehensive discussion of these effects could be found in the book by Avdeef [22]. 

Unger, S.H., Cheung, P.S., Chiang, G.H. and Cook, J.R. (1986) RP-HPLC determination of 1-octanol. Partition and distribution coefficients experience and results, in Partition Coefficient Determination and Estimation (eds W.J. Dunn III, J.H. Block and R.S. Pearlman), Pergamon Books, New York pp. 69-81. 

The most common method for determining partition and distribution coefficients is the shake flask method. In this technique, the candidate drug is shaken between octanol (previously shaken together to presaturate each phase with the other) and water layers, from which an aliquot is taken and analyzed using UV absorption, HPLC or titration. In terms of experimental conditions, the value of the partition coefficient obtained from this type of experiment is affected by such factors as temperature, insufficient mutual phase saturation, pH and buffer ions and their concentration, as well as the nature of the solvents used and solute examined (Dearden and Bresnen 1988). 

F. H. Clarke and N. M. Cahoon, ). Pharm. Sci., 76, 611 (1987). Ionization Constants by Curve Fitting Determination of Partition and Distribution Coefficients of Acids and Bases and Their Ions. 

Partition and Distribution Coefficients of Solutes and Drugs in Brush Border Membrane Vesicles. 

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