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


CONCLUSIONS
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.
Department of Medicinal Chemistry, Faculty of Pharmacy and Biochemistry, University of Zagreb, Zagreb. Croatia.
Hrvoje
H
Rimac
Institute of Clinical Laboratory Diagnostics, Osijek University Hospital, 31000 Osijek. Croatia.
Željko
Ž
Debeljak
Department of Medicinal Chemistry, Faculty of Pharmacy and Biochemistry, University of Zagreb, Zagreb. Croatia.
Mirza
M
Bojić
Sanofi Genzyme, Boston, MA. United States.
Larisa
L
Miller
D000818:Animals; D001665:Binding Sites; D004347:Drug Interactions; D006801:Humans; D007700:Kinetics; D062105:Molecular Docking Simulation; D004364:Pharmaceutical Preparations / Q000737:chemistry / Q000378:metabolism*; D011485:Protein Binding; D012709:Serum Albumin / Q000737:chemistry / Q000378:metabolism*
D004364:Pharmaceutical Preparations; D012709:Serum Albumin
Human serum albumin; Sudlow’s site I; Sudlow’s site II; drug design; drug displacement; free concentration; pharmacokinetic interactions