Wahed Amer, Pollard John, Wells Alice, Dasgupta Amitava
Department of Pathology and Laboratory Medicine, University of Texas-Houston Medical School, Houston, Texas 77030, USA.
J Clin Lab Anal. 2003;17(5):179-83. doi: 10.1002/jcla.10090.
DanShen is a Chinese medicine that is used to treat cardiovascular disorders. DanShen is moderately to strongly protein bound, mainly to albumin. Because impaired protein binding of albumin-bound drugs in uremia has been reported, we studied protein binding of DanShen by measuring the digoxin-like immunoreactive component of this Chinese medicine. We observed a significantly higher percentage of free fraction of DanShen in uremic sera in vitro. Impaired protein binding of DanShen was also observed in sera from patients with liver disease, who had elevated concentrations of bilirubin. Treating uremic sera with activated charcoal significantly improved the protein binding of DanShen, indicating that uremic compounds are responsible for the impaired protein binding of DanShen. On the other hand, when various amounts of bilirubin were added to aliquots of the normal pool supplemented with DanShen, we observed only a modest displacement of DanShen from the protein-binding sites by bilirubin, indicating that hypoalbuminemia may play a major role in impaired protein binding of DanShen in sera with elevated bilirubin concentrations. We conclude that protein binding of DanShen is lower in uremic sera and in sera with elevated bilirubin concentrations.
丹参是一种用于治疗心血管疾病的中药。丹参与蛋白质有中度至高度的结合，主要与白蛋白结合。由于已有报道称尿毒症患者中与白蛋白结合的药物的蛋白质结合受损，我们通过测量这种中药中地高辛样免疫反应成分来研究丹参的蛋白质结合情况。我们在体外观察到尿毒症血清中丹参的游离分数百分比显著更高。在患有肝病且胆红素浓度升高的患者的血清中也观察到丹参的蛋白质结合受损。用活性炭处理尿毒症血清可显著改善丹参的蛋白质结合，这表明尿毒症化合物是丹参蛋白质结合受损的原因。另一方面，当向添加了丹参的正常血清样本中加入不同量的胆红素时，我们仅观察到胆红素使丹参从蛋白质结合位点上有适度的置换，这表明低白蛋白血症可能在胆红素浓度升高的血清中丹参蛋白质结合受损中起主要作用。我们得出结论，丹参在尿毒症血清和胆红素浓度升高的血清中的蛋白质结合较低。
