Comparison of graphical and computerized methods for calculating binding parameters for two strongly bound drugs to human serum albumin.

The determination of drug-protein binding parameters (n's and K's) can lead to important information on the required therapeutic dosage regimen and possible clinical complications associated with competitive displacement of one drug by a concurrently administered agent. Graphical and computer estimates of the data are often incorrectly formulated, and and seldom are adequate data obtained at low binding ratios. Commonly used graphical procedures, inadequately formulated computer methods, and a statistically correct computer method were used to compare results obtained from a circular dichroic examination of dicumarol-human serum albumin and fenoprofen-human serum albumin interactions. Literature binding constants for dicumarol-albumin range from 1 X 10(5) to 30 times that figure, and it is shown here that a wide range in parameter estimates may be obtained depending on the method of data analysis. The parameter estimates in the case of fenoprofen-albumin are even more variable.