Honoré B, Brodersen R
Mol Pharmacol. 1984 Jan;25(1):137-50.
Binding equilibria of 12 nonsteroidal, anti-inflammatory substances, salicylic acid, diflunisal, phenylbutazone, azapropazone, fenbufen, biphenylacetic acid, naproxen, flurbiprofen, ibuprofin, diclofenac, indomethacin, and benoxaprofen, to defatted human serum albumin has been investigated at 37 degrees, pH 7.4, in a sodium phosphate buffer, 66 mM, by means of equilibrium dialysis and, in case of salicylic acid, by dialysis rate determinations. Cobinding of each of these drugs with monoacetyl-4,4'-diaminodiphenyl sulfone, warfarin, and diazepam has been studied by measuring dialysis rates of the last-mentioned ligands. Cobinding of each drug with bilirubin was investigated by two techniques, equilibrium dialysis against albumin with and without bilirubin, and by measuring rates of oxidation of free bilirubin with hydrogen peroxide and peroxidase. Results were analyzed in quantitative terms. The use of a site-oriented description versus a stoichiometric analysis is discussed. The stoichiometric description is preferred for the following reasons: (a) Simple relations exist between the percentage of bound drug at low drug concentrations and the first stoichiometric binding constant. (b) The stoichiometric description does not imply that preformed binding sites are present in the albumin molecule. (c) A quantitative, stoichiometric analysis of multiple cobinding of two ligands is possible.
在37℃、pH 7.4、66 mM磷酸钠缓冲液中，采用平衡透析法研究了12种非甾体抗炎物质，即水杨酸、二氟尼柳、保泰松、阿扎丙宗、芬布芬、联苯乙酸、萘普生、氟比洛芬、布洛芬、双氯芬酸、吲哚美辛和贝诺洛芬与脱脂人血清白蛋白的结合平衡；对于水杨酸，还通过测定透析速率进行了研究。通过测量上述配体的透析速率，研究了这些药物与单乙酰-4,4'-二氨基二苯砜、华法林和地西泮的共结合情况。采用两种技术研究了每种药物与胆红素的共结合情况：一种是用含有和不含胆红素的白蛋白进行平衡透析；另一种是通过测定过氧化氢和过氧化物酶存在下游离胆红素的氧化速率。对结果进行了定量分析。讨论了使用基于位点的描述与化学计量分析的情况。化学计量描述更可取，原因如下：(a) 在低药物浓度下，结合药物的百分比与第一个化学计量结合常数之间存在简单关系。(b) 化学计量描述并不意味着白蛋白分子中存在预先形成的结合位点。(c) 对两种配体的多重共结合进行定量化学计量分析是可能的。
