Steele W H, Boobis S W, Moore M R, Goldberg A, Brodie M J, Summer D J
Eur J Clin Pharmacol. 1978 Jun 19;13(4):309-13. doi: 10.1007/BF00716368.
(1) Plasma protein binding of salicylate was studied in 14 patients with cutaneous hepatic porphyria (CHP) and 11 normal subjects using ultrafiltration with centrifugation (membrane cones) and continuous ultrafiltrations. (2) Albumin and haemoglobin levels were significantly reduced in patients with CHP, and salicylate binding by ultrafiltration/centrifugation was 65% compared with 84% in normal subjects. (3) Plasma porphyrin levels were raised, but did not correlate with salicylate binding, and protoporphyrin or uroporphyrin added to plasma did not alter the amount of drug bound. (4) Palmitate added to plasma reduced salicylate binding by 9 to 20% but a crossover of patient and normal plasma proteins and ultrafiltrates confirmed that no other ultrafiltrable metabolites present in patient plasma appeared to cause decreased binding. (5) Scatchard plots obtained by continuous ultrafiltration for normal and patient plasma showed a reduction in the number of primary and secondary binding sites and an increase in the intrinsic association constants for both these sites. (6) It was concluded that the decreased salicylate binding in CHP was due to a reduced albumin concentration and altered salicylate albumin interaction.
(1) 采用离心超滤法（膜锥）和连续超滤法，对14例皮肤性肝卟啉病（CHP）患者和11名正常受试者的水杨酸盐血浆蛋白结合情况进行了研究。(2) CHP患者的白蛋白和血红蛋白水平显著降低，通过超滤/离心法测得的水杨酸盐结合率在患者中为65%，而在正常受试者中为84%。(3) 血浆卟啉水平升高，但与水杨酸盐结合无关，向血浆中添加原卟啉或尿卟啉不会改变药物结合量。(4) 向血浆中添加棕榈酸盐可使水杨酸盐结合率降低9%至20%，但患者和正常血浆蛋白及超滤液的交叉实验证实，患者血浆中不存在其他可超滤代谢产物似乎不会导致结合率降低。(5) 通过连续超滤法对正常和患者血浆获得的Scatchard图显示，一级和二级结合位点数量减少，这两个位点的内在缔合常数增加。(6) 得出的结论是，CHP中水杨酸盐结合减少是由于白蛋白浓度降低以及水杨酸盐与白蛋白相互作用改变所致。
