Impaired protein binding of Chinese medicine DanShen in uremic sera and sera with hyperbilirubinemia: rapid assessment of total and free DanShen concentrations using the fluorescence polarization immunoassay for digoxin.
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.
Wahed
Amer
A
Department of Pathology and Laboratory Medicine, University of Texas-Houston Medical School, Houston, Texas 77030, USA.
Pollard
John
J
Wells
Alice
A
Dasgupta
Amitava
A
D000085:Acetates / Q000737:chemistry; D001557:Benzenesulfonates; D001663:Bilirubin / Q000097:blood; D001798:Blood Proteins / Q000187:drug effects / Q000378:metabolism; D002606:Charcoal / Q000737:chemistry; D003401:Creatine / Q000097:blood; D004077:Digoxin / Q000097:blood*; D004365:Drugs, Chinese Herbal / Q000009:adverse effects / Q000378:metabolism; D016231:Fluorescence Polarization Immunoassay / Q000379:methods; D006801:Humans; D006932:Hyperbilirubinemia / Q000097:blood*; D010618:Phenanthrolines / Q000009:adverse effects / Q000097:blood* / Q000378:metabolism; D011485:Protein Binding; D012459:Salicylates / Q000737:chemistry; D027561:Salvia miltiorrhiza / Q000737:chemistry; D012709:Serum Albumin / Q000032:analysis; D014511:Uremia / Q000097:blood*
D000085:Acetates; D001557:Benzenesulfonates; D001798:Blood Proteins; D004365:Drugs, Chinese Herbal; D010618:Phenanthrolines; D012459:Salicylates; D012709:Serum Albumin; D002606:Charcoal; C028972:dan-shen root extract; D004077:Digoxin; C007650:ethyl acetate; C003366:sulfosalicylic acid; D003401:Creatine; D001663:Bilirubin