RT Journal Article
SR Electronic
T1 Alternative Models for the Analysis of Drug-Protein Binding
JF Molecular Pharmacology
JO Mol Pharmacol
FD American Society for Pharmacology and Experimental Therapeutics
SP 387
OP 399
VO 13
IS 3
A1 JOHN E. FLETCHER
A1 ARTHUR A. SPECTOR
YR 1977
UL http://molpharm.aspetjournals.org/content/13/3/387.abstract
AB Mathematical models that are used to describe experimentally obtained drug-protein binding data often exhibit serious limitations. These limitations are demonstrated by a thorough examination of the binding of salicylate to human serum albumin. It is shown that simple models with nonintegral coefficients are inadequate for the interpretation of such binding data. A generalized mathematical formulation that includes both the Scatchard and stepwise equilibrium binding models is derived. This formulation is simpler to fit to data than the stepwise formulation, yet is not restricted to the Scatchard assumption of independent and noninteracting binding sites. This alternative formula is appropriate for the analysis of all equilibrium binding data. Even with this generalized mathematical formulation and sophisticated computerized fitting techniques, it is not possible to define precisely a single binding model for the salicylate binding data. The utility of model fitting in such a case is discussed, and procedures are demonstrated that characterize the information that can be obtained. ACKNOWLEDGMENTS The authors gratefully acknowledge the generous cooperation of Dr. Roland F. Mais of the Veterans Administration Hospital, Neuropharmacology Research Service, Hines, Illinois, in supplying the data used to illustrate the methodology in this paper. We also acknowledge the technical assistance of Mrs. Elizabeth Fleetwood in the preparation of the manuscript.