| Abstrakt: |
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 semiempirical calculations forS. Multidimensional plots are developed with the physical constantsSandPalong thexandyaxes and with a biological response, e.g. IC50or ED50, along thezaxis. Other attributes, e.g. bioavailability or biodistribution, can be added by color coding, 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, EC50)] can be correlated for drug series comprising large numbers of compounds. |
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