ESTIMATION AND CORRELATION OF DRUG WATER SOLUBILITY WITH PHARMACOLOGICAL PARAMETERS REQUIRED FOR BIOLOGICAL-ACTIVITY

A procedure for estimating the molar water solubility (S) for a series of structurally related drug compounds is presented. HPLC methods for the determination of partition coefficients (P) are combined with sem iempirical calculations for S. Multidimensional plots ari developed wi th the physical constants S and P along the x and y axes and with a bi ological response, e.g. IC50 Or ED(50), along the z axis. Other attrib utes, e.g. bioavailability or biodistribution, can be added by color c oding, shading, or numbering. Since the methods have a high thoughput capability, parameters governing the events leading to pharmacological action [i.e. gastrointestinal dissolution (S), absorption (P), blood level (bioavailability), and biological action (IC50, EG(50))] can be correlated for drug series comprising large numbers of compounds.