Otagiri M, Maruyama T, Imai T, Suenaga A, Imamura Y
J Pharm Pharmacol. 1987 Jun;39(6):416-20. doi: 10.1111/j.2042-7158.1987.tb03412.x.
The interaction of warfarin with human alpha 1-acid glycoprotein (alpha 1-AGP) and human albumin (HA) has been investigated using fluorescence and circular dichroism techniques. The fluorescence of warfarin is greatly enhanced following binding to alpha 1-AGP or HA, the binding constant for a single site being estimated by the Scatchard method. The binding constants for the two serum proteins are similar, but the thermodynamic parameters differ. The binding constants increase as the pH is raised to 9.0. Various basic drugs, such as chlorpromazine, propranolol and imipramine, markedly inhibited the binding of warfarin to alpha 1-AGP. But, some acidic drugs, including phenylbutazone, effectively displaced warfarin bound to HA. The difference in CD spectra observed for alpha 1-AGP and HA indicated that the drug-binding sites of the two proteins might have different asymmetries. It thus appears that the mode of interaction of warfarin with the two proteins differs.
利用荧光和圆二色性技术研究了华法林与人α1-酸性糖蛋白（α1-AGP）和人白蛋白（HA）之间的相互作用。华法林与α1-AGP或HA结合后，其荧光显著增强，通过Scatchard方法估算单个位点的结合常数。两种血清蛋白的结合常数相似，但热力学参数不同。随着pH值升高至9.0，结合常数增大。各种碱性药物，如氯丙嗪、普萘洛尔和丙咪嗪，显著抑制华法林与α1-AGP的结合。但是，一些酸性药物，包括保泰松，能有效置换结合在HA上的华法林。观察到的α1-AGP和HA的圆二色光谱差异表明，这两种蛋白质的药物结合位点可能具有不同的不对称性。因此，华法林与这两种蛋白质的相互作用模式似乎有所不同。
