Theoretical and experimental studies of the plasma protein binding of high affinity binding drugs
AuthorLee, Hui-Chih, 1963-
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PublisherThe University of Arizona.
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AbstractA disadvantage of traditional equilibrium dialysis for highly protein bound drugs is the analytically low drug concentration found on the buffer side. We propose to replace a certain percentage of buffer with plasma containing drug in order to increase the total drug concentration on the buffer side. Computer simulations were performed to examine the effects of the percentage of plasma replacement of the buffer upon the increase of the total drug concentration on the buffer side after equilibrium dialysis. Further simulation results indicated that the development of a concise equation estimating the drug's equilibrium association binding constant (Ka) was feasible. Two high binding drugs, diazepam and nortriptyline, were examined to verify the advantages offered by the new proposed method and their Ka values were computed using the experimental results and the mathematical equation developed. The resulting data agreed well with theoretical predictions.
Degree ProgramGraduate College