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Published on:9th Feb, 2015
Indian Journal of Pharmaceutical Research and Education, 2015; 49(3):225-230
Pharmaceutical Research | doi:10.5530/ijper.49.3.8

Warfarin Binding to Native and Structurally-Altered Human Serum Albumins


Authors and affiliation (s):

Nasim Sakhaei, Adyani Azizah Abdul Halim and Saad Tayyab*

Biomolecular Research Group, Biochemistry Programme, Institute of Biological Sciences, University of Malaya 50603 Kuala Lumpur, MALAYSIA

Abstract:

Background and Purpose: Interaction of a drug with the carrier protein in the circulation determines its distribution, free or bound concentration and metabolism. Structural alteration in the major transport protein, human serum albumin (HSA) under several pathological conditions may affect its drug binding ability. The objective of the present investigation was to explore the binding of warfarin to structurally-altered HSA. Methods: Effect of urea, a denaturant on the interaction of warfarin with HSA was investigated using fluorescence spectroscopy. Results and Discussion: Fluorescence spectra of native HSA were characterized by the presence of an emission maximum around 339 and 343 nm, when excited at 280 and 295 nm, respectively. Warfarin binding to HSA was marked by a significant decrease in the fluorescence intensity and red shift in the emission maximum, being more pronounced at lower (1-5 μM) and smaller at higher (10-40 μM) drug concentrations. Presence of urea affected these signals to a significant extent even at lower concentrations. A significant decrease in both quenching and binding constants with increasing urea concentrations, suggested separation of excited fluorophore (Trp) of HSA and warfarin leading to the loss in its drug binding ability.

Key words: Drug Binding, Fluorescence Quenching, Human Serum Albumin, Urea, Warfarin.

 

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The Official Journal of Association of Pharmaceutical Teachers of India (APTI)
(Registered under Registration of Societies Act XXI of 1860 No. 122 of 1966-1967, Lucknow)

Indian Journal of Pharmaceutical Education and Research (IJPER) [ISSN-0019-5464] is the official journal of Association of Pharmaceutical Teachers of India (APTI) and is being published since 1967.

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