Summary
The binding to human albumin of four acidic drugs, acenocoumarin, sodium chlorophenoxyisobutyrate, phenylbutazone and warfarin, has been measured by equilibrium dialysis and ultrafiltration at 37°C and pH 7.4. The affinity constants and numbers of binding sites for each drug were then calculated according to the law of mass action. With the aid of these values, it was possible to estimate the percentage binding of each drug after a therapeutic dose and assuming an albumin concentration of 40 g/l. The results obtained were identical to those previously measuredin vivo.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Aggeler, P.M., O'Reilly, R.A., Leong, L., Kowitz, P.E.: Potentiation of anticoagulant effect of warfarin by phenylbutazone. New Engl. J. Med.276, 496–501 (1967)
Beaulieu, E.E., Raynaud, J.P.: A proportion graph method for measuring binding systems. Europ. J. Biochem.13, 293–304 (1970)
Branstad, J.O., Meresaar, V., Agren, A.: Complex formation between macromolecules and drugs. VII — The binding of some barbiturates to human serum albumin (HSA) at varying pH. Acta Pharm. Suecica9, 129–134 (1972)
Bridgman, J.F., Rosen, S.M., Thorp, J.M.: Complications during clofibrate treatment of nephrotic-syndrome hyperlipoproteinaemia. Lancet1972 I, 506–509
Burns, J.J., Rose, R.K., C7enkin, T., Goldman, A., Shubert A., Brodie, B.B.: The physiological disposition of phenylbutazone (butazolidin) in man and a method for its estimation in biological material. J. Pharmacol. (Kyoto)109, 346–357 (1953)
Chignell, C.F.: Circular dichroism studies of drug-protein complexes. Life Sci.7, 1181–1186 (1968)
Chignell, C.F.: Optical studies of drug-protein complexes. IV. The interaction of warfarin and dicoumarol with human serum albumin. Molec. Pharmacol.6, 1–12 (1970)
Chignell, C.F., Starkweather, D.K.: Species differences in the binding of phenylbutazone to plasma albumin. Pharmacology5, 235–244 (1971)
Edsall, J.T., Wyman, J.: Biophysical Chemistry. Vol. I, p. 613. New York: Academic Press Inc 1958
Fletcher, J.E., Spector, A.A.: A procedure for computer analysis of data from macromolecule — ligand binding studies. Computers biomed. Res.2, 164–175 (1968)
Garten, S., Wosilait, W.D.: Comparative study of the binding of coumarin anticoagulants and serum albumin. Biochem. Pharmacol.20, 1661–1668 (1971)
Garten, S., Wosilait, W.D.: An analysis of the binding of coumarin anticoagulants by human serum albumin. Comp. gen. Pharmacol.3, 83–88 (1972)
Goldstein, A.: The interactions of drugs and plasma proteins. Pharmacol. Rev.1, 102–165 (1949)
Meyer, M.C., Guttman, D.E.: The binding of drugs by plasma proteins. J. pharm. Sci.57, 895–918 (1968)
MacQueen, E. G.: Displacement from protein binding of sulphormethoxine by phenylbutazone using invivo dialysis in rats. Brit. J. Pharmacol.36, 229–234 (1969)
O'Reilly, R.A.: Interaction of the anticoagulant drug warfarin and its metabolites with human plasma albumin. J. clin. Invest.48, 193–202 (1969)
O'Reilly, R.A.: Interaction of several coumarin compounds with human and canine plasma albumin. Molec. Pharmacol.7, 209–218 (1971)
O'Reilly, R.A., Aggeler, P.M., Hoag, M.S., Leong, L.: Studies on the coumarin anticoagulant drugs: the assay of warfarin and its biologic application. Thrombos. Diathes. haemorrh. (Stuttg.)8, 82–95 (1962)
Rosenthal, H.E.: A graphic method for the determination and presentation of binding parameters in a complex system. Analyt. Biochem.20, 525–532 (1967)
Rudman, D., Bixler II, T.J., Del Rio, A.E.: Effect of free fatty acids on binding of drugs by bovine serum albumin, by human serum albumin and by rabbit serum. J. Pharmacol. (Kyoto)176, 261–272 (1971)
Scatchard, G.: The attraction of proteins for small molecules and ions. Ann. N.Y. Acad. Sci.51, 660–672 (1949)
Sellers, E.M., Koch-Weser, J.: Displacement of warfarin from human albumin by diazoxide and ethacrynic, mefenamic and nalidixic acids. Clin. Pharmacol. Ther.11, 524–529 (1970)
Sheppey, G.C.: Minros programm of minimisation. C.E.R.N. ed. (1970)
Solomon, H.M., Schrogie, J.J.: The effect of various drugs on the binding of warfarin14C to human albumin. Biochem. Pharmacol.16, 1219–1226 (1967)
Solomon, H.M., Schrogie, J.J., Williams, D.: The displacement of phenylbutazone14C and warfarin14C from human albumin by various drugs and fatty acids. Biochem. Pharmacol.17, 143–151 (1968)
Sudlow, G., Birkett, D.J., Wade, D.N.: Spectroscopic techniques in the study of protein binding. The use of 1 — anilino — 8 — naphtalenesulfonate as a fluorescent probe for the study of the binding of iophenoxic and iopanoic acids to human serum albumin. Molec. Pharmacol.9, 649–657 (1973)
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Tillement, J.P., Zini, R., d'Athis, P. et al. Binding of certain acidic drugs to human albumin: Theoretical and practical estimation of fundamental parameters. Eur J Clin Pharmacol 7, 307–313 (1974). https://doi.org/10.1007/BF00560349
Received:
Revised:
Issue Date:
DOI: https://doi.org/10.1007/BF00560349