Studies on absorption and excretion of drugs. XI. Relation between chemical structure and absorption rate. (3). Intramolecular interaction constant, additivity rule and prediction for intestinal absorption rate coefficient.

Abstract

It was expected that the absorption rate coefficient of the foreign organic compound was, as a first approximation, a simple additive function of its substituent groups and that the absorption rate coefficient should be predicted from the additivity rule. Furthermore, the following relationship for the intestinal absorption rate of foreign organic compounds was expected from the application of the activated diffusion model, the transition state theory and the formal treatment based on the extrathermodynamic relationships, log kRS(i)…s(j)/kRS(i)s(j)=constant where kRS(i)…s(j) or kRS(i)s(j) denotes the absorption rate coefficient for the compound with or without the intramolecular interaction, respectively. The perfusion experiments through the small intestine of anesthetized rats for various benzene derivatives with or without intramolecular interaction were carried out. The logarithmic plots of the residual ratio against the perfusion time gave straight lines and from the slopes the absorption rate coefficients were obtained. The results indicate that the absorption rate coefficient can be essentially predicted from the additivity rule and that the values of log kRS(i)…s(j)/kRS(i)s(j) for a given combination of interacting groups have a proper value which is called the intramolecular interaction constant.