Physicochemical and in-vitro biological studies on the possible association between theophylline and ethylenediamine...

The possible association in solution between the components of aminophylline, theophylline and ethylenediamine, has been studied using physicochemical and biochemical techniques. Addition of ethylenediamine to solutions of theophylline caused characteristic changes in its u.v. and 13C-n.m.r. spectra, which were due solely to the pH change, and not to any molecular association between the molecules in solution. Both compounds crossed the erythrocyte membrane extensively from plasma or 0.9% NaCl and had no influence on each other's behaviour. Theophylline partitioned approximately equally between octanol and pH 7.4 phosphate buffer, while ethylenediamine remained in the aqueous phase. Again, neither compound affected the properties of the other. Theophylline was reversibly bound to plasma protein, the extent of which was dependent upon the temperature used for equilibrium dialysis. However, ethylenediamine was not bound to plasma protein, and did not alter the binding of theophylline. These data show that the components of aminophylline behave independently in solution, and suggest that there is no association between theophylline and ethylenediamine in biological systems.