title: Binding of aprindine and moxaprindine to human serum, alpha 1-acid glycoprotein and serum of healthy and diseased humans.
abstract: A comparison was made between the binding of the anti-arrhythmic agents aprindine and moxaprindine to human serum, to human serum albumin (HSA), to alpha 1-acid glycoprotein (alpha 1-AGP) and to a mixture of HSA and alpha 1-AGP. In serum from healthy volunteers (n = 4) the binding of aprindine-HCl 5 micrograms/ml (13.8 microM) was 93.8% (SD +/- 1.0), and that of moxaprindine-HCl 5 micrograms/ml (12.8 microM) was 94.15 (SD +/- 1.1). Their binding to the mixture of alpha 1-AGP and albumin approximated their binding to serum. For alpha 1-AGP, the binding was similar for both compounds, whereas for HSA the binding of aprindine was more pronounced than that of moxaprindine: for both products the affinity coefficient for binding to alpha 1-AGP was about 100 times greater than that for binding to albumin. In serum from rheumatoid patients and from patients with renal failure a small but significant increase in binding of aprindine and moxaprindine was observed, approximately 1%. Increased and decreased binding was seen in serum from cirrhotic patients; for example, for aprindine the range in cirrhosis was 96.7%-79.8%, and the range in controls was 95.0%-92.4%. Free drug fraction and alpha 1-AGP concentration were inversely correlated. The results show that alpha 1-AGP plays an important role in the binding of aprindine and moxaprindine, and that alteration in the binding of the two compounds in disease states to a large extent can be explained by changes in serum alpha 1-AGP concentration.
mesh_terms: D001073:Aprindine / Q000031:analogs & derivatives / Q000097:blood*; D001172:Arthritis, Rheumatoid / Q000097:blood; D006801:Humans; D007192:Indenes / Q000097:blood*; D007676:Kidney Failure, Chronic / Q000097:blood; D008103:Liver Cirrhosis / Q000097:blood; D009961:Orosomucoid / Q000378:metabolism*; D011485:Protein Binding; D012709:Serum Albumin / Q000378:metabolism*
chemical_list: D007192:Indenes; D009961:Orosomucoid; D012709:Serum Albumin; C023489:moxaprindine; D001073:Aprindine