Relationship between the solubility parameter and the binding of drugs by plasma proteins

An equation, based on regular solution theory, was used to relate the solubility parameter to the binding of drugs by plasma proteins. The equation was tested on a homologous series and a good correlation was found. Sulfonamides showed maximum binding when their solubility parameters were similar to the solubility parameters of the amino acids situated in a sequence with one tryptophan residue. This observation supports the assumption that this sequence is the primary binding site for the sulfonamides. Binding peaks were also found at solubility parameters in other drug series corresponding to the solubility parameters of human serum albumin (HSA) or bovine serum albumin (BSA) amino acids. It is suggested that the solubility parameter could be used to predict the binding of drugs to plasma proteins.