- 作者: Chung-Eun Ha; Charles E. Petersen; David S. Park; Krshna Harohalli; Nadhipuram V. Bhagavan
- 作者服務機構: Department of Biochemistry and Biophysics, John A. Burns School of Medicine, University of Hawaii, Honolulu, Hawaii, USA
- 中文摘要: --
- 英文摘要: Ethanol effects on warfarin binding to human serumalbumin (HSA) have been studied by equilibrium dialysisand fluorescence methods at pH 7.4 in phosphate-buff-ered saline at 37℃. In the presence of various amountsof ethanol fluorescence intensity of bound warfarin de-creased significantly but this intensity reduction was notsolely from displacement of bound warfarin from HSA.By comparing fluorescence and equilibrium dialysis datawe concluded that fluorescence intensity reduction ofwarfarin was mainly the result of changes in the sur-rounding environment of the warfarin binding site byethanol interaction with HSA and that displacement ofbound warfarin was not significant compared to the fluo-rescence intensity changes. The dissociation constant ofwarfarin binding to HSA decreased with an increasingamount of ethanol. From the changes in fluorescenceintensity upon warfarin binding to HSA with the pres-ence of ethanol ranging from 0 to 5.0%the following dis-sociation constants (Kd) were determined: 0% ethanol5.39±0.2μM, 0.1% ethanol 5.86±0.1μM, 0.3% ethanol5.83±0.2μM, 0.5% ethanol 6.76±0.1μM, 1% ethanol7.01±0.1μM, 3% ethanol 9.9±0.7μM, 5% ethanol13.01±0.1μM. From the equilibrium dialysis with thesame ranges of ethanol presence the following Kd val-ues were obtained: 0% ethanol 6.62±1.6μM, 0.1% eth-anol 6.81±1.1μM, 0.3% ethanol 8.26±2.5μM, 0.5%ethanol 8.86±1.9μM, 1% ethanol 11.01±4.2μM, 3%ethanol 20.75±2.4μM, 5% ethanol 21.67±2.2μM. Theresults suggest that warfarin bound to HSA was dis-placed by ethanol. These data indicate that ethanolinfluence on warfarin binding to HSA may alter the phar-macokinetics of warfarin.
- 中文關鍵字: --
- 英文關鍵字: --