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.

• Authors: O Teirlynck, F M Belpaire, F Andreasen
• Journal: European journal of clinical pharmacology (Eur J Clin Pharmacol) Vol. 21 Issue 5 Pg. 427-31 ( 1982) ISSN: 0031-6970 [Print] Germany
• PMID: 7075647 (Publication Type: Journal Article)

Chemical References

• Indenes
• Orosomucoid
• Serum Albumin
• moxaprindine
• Aprindine

Topics

• Aprindine (analogs & derivatives, blood)
• Arthritis, Rheumatoid (blood)
• Humans
• Indenes (blood)
• Kidney Failure, Chronic (blood)
• Liver Cirrhosis (blood)
• Orosomucoid (metabolism)
• Protein Binding
• Serum Albumin (metabolism)