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Displacement of Drugs from Human Serum Albumin: From Molecular Interactions to Clinical Significance

[ Vol. 24 , Issue. 18 ]

Author(s):

Hrvoje Rimac, Željko Debeljak, Mirza Bojić and Larisa Miller   Pages 1930 - 1947 ( 18 )

Abstract:


Background: Human serum albumin (HSA) is the most abundant protein in human serum. It has numerous functions, one of which is transport of small hydrophobic molecules, including drugs, toxins, nutrients, hormones and metabolites. HSA has the ability to interact with a wide variety of structurally different compounds. This promiscuous, nonspecific affinity can lead to sudden changes in concentrations caused by displacement, when two or more compounds compete for binding to the same molecular site.

Objective: It is important to consider drug combinations and their binding to HSA when defining dosing regimens, as this can directly influence drug’s free, active concentration in blood.

Conclusion: In present paper we review drug interactions with potential for displacement from HSA, situations in which they are likely to occur and their clinical significance. We also offer guidelines in designing drugs with decreased binding to HSA.

Keywords:

Human serum albumin, drug displacement, pharmacokinetic interactions, free concentration, drug design, Sudlow’s site I, Sudlow’s site II.

Affiliation:

Department of Medicinal Chemistry, Faculty of Pharmacy and Biochemistry, University of Zagreb, Zagreb, Institute of Clinical Laboratory Diagnostics, Osijek University Hospital, 31000 Osijek, Department of Medicinal Chemistry, Faculty of Pharmacy and Biochemistry, University of Zagreb, Zagreb, Sanofi Genzyme, Boston, MA



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