Binding of tolbutamide to glycated human serum albumin

K. S. Joseph, Jeanethe Anguizola, David S. Hage

Research output: Contribution to journalArticle

61 Citations (Scopus)

Abstract

The presence of elevated levels of glucose in blood during diabetes can lead to the non-enzymatic glycation of serum proteins such as human serum albumin (HSA). This study examined the changes that occur in binding of the sulfonylurea drug tolbutamide to HSA as the level of glycation for this protein was increased. High-performance affinity chromatography was used in this work along with columns containing various preparations of in vitro glycated HSA. It was found in frontal analysis experiments that the binding of tolbutamide with all of the tested preparations of glycated HSA could be described by a two-site model involving both strong and weak affinity interactions. The association equilibrium constants (Ka) for tolbutamide at its high affinity sites on glycated HSA were in the range of 0.8-1.2×105M-1 and increased by 1.4-fold in going from normal HSA to mildly glycated HSA. It was found through competition studies that tolbutamide was binding at both Sudlow sites I and II on the glycated HSA, in agreement with previous studies. The Ka for tolbutamide at Sudlow site II increased by 1.1- to 1.4-fold in going from normal HSA to glycated HSA. At Sudlow site I, the Ka for tolbutamide increased by 1.2- to 1.3-fold in going from normal HSA to the glycated HSA samples. This information demonstrates the effects that glycation can have on drug interactions on HSA and should provide a better quantitative understanding of how the protein binding of tolbutamide in serum may be affected for individuals with diabetes.

Original languageEnglish (US)
Pages (from-to)426-432
Number of pages7
JournalJournal of Pharmaceutical and Biomedical Analysis
Volume54
Issue number2
DOIs
StatePublished - Jan 25 2011

Fingerprint

Tolbutamide
Serum Albumin
Medical problems
Drug interactions
Affinity chromatography
Equilibrium constants
Drug Interactions
Affinity Chromatography
Protein Binding
Blood Glucose
Blood Proteins

Keywords

  • Drug-protein binding
  • Glycation
  • High-performance affinity chromatography
  • Human serum albumin
  • Tolbutamide

ASJC Scopus subject areas

  • Analytical Chemistry
  • Pharmaceutical Science
  • Drug Discovery
  • Spectroscopy
  • Clinical Biochemistry

Cite this

Binding of tolbutamide to glycated human serum albumin. / Joseph, K. S.; Anguizola, Jeanethe; Hage, David S.

In: Journal of Pharmaceutical and Biomedical Analysis, Vol. 54, No. 2, 25.01.2011, p. 426-432.

Research output: Contribution to journalArticle

Joseph, K. S. ; Anguizola, Jeanethe ; Hage, David S. / Binding of tolbutamide to glycated human serum albumin. In: Journal of Pharmaceutical and Biomedical Analysis. 2011 ; Vol. 54, No. 2. pp. 426-432.
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