Absorption and excretion of drugs. XXXI. On the relationship between partition coefficients and chemical structures of barbituric acid derivatives.

Abstract

The partition coefficients, which are known to be an influencing factor in physiological dispositions of drugs, were investigated systematically with three series of barbituric acid derivatives. From the results obtained, the concentration dependence of partitioning, and specific association of molecules in both aqueous and solvent phase were not observed. The latter was supported also by the computed degree of association obtained from the diffusion data. A logarithmic relationship between partition coefficients to two different organic solvents was found to exist, and this relationship provides a useful method or information to elucidate the characterizations of partitioning mechanism and their relation to the absorption phenomena. In respect to the effect of chemical structure on partition equilibrium, it was confirmed with all derivatives and solvent systems that the partition coefficients were prediced from the two parameters of the substituent at 5-position of barbituric acid ring, namely, the mass of the substituent in number of carbon atoms, and Taft's polar constant using the equation related to Hammett's rule.