The protein binding of timegadine determined by equilibrium dialysis.

Abstract

The protein binding of timegadine to albumin, serum, plasma and plasma enriched with the acute phase reactants alpha 1‐acid glycoprotein, alpha 1‐anti‐trypsin and C‐reactive protein was determined by equilibrium dialysis. The effects of other analgesic and anti‐ inflammatories (indomethacin, ketoprofen, paracetamol and sodium salicylate) and other basic drugs (disopyramide, lignocaine, propranolol and quinidine) on the binding of timegadine were also determined. Timegadine binding was concentration‐dependent up to 0.5 micrograms/ml, but independent above this level up to 10.0 micrograms/ml, the mean and standard error being 93.8 +/‐ 0.5%. Albumin accounted for only 32.4% of timegadine bound to plasma. Plasma enrichment with the acute phase reactants led to significant increases in timegadine binding. Simultaneous dialysis with other drugs caused significant decreases in timegadine binding.

The plasma protein binding of basic drugs.

“…Binding to other proteins Lipoproteins, have been described to bind some basic drugs such as amitriptyline and nortriptyline (Pike et al, 1983). Complement C3 has been reported to be related to imipramine binding (Kristensen, 1983) and the plasma protein binding of new non-steroidal anti-inflammatory agent, timegadine, was increased by enrichment of plasma with C reactive protein, al-antitrypsin and AAG (George et al, 1984). The clinical relevance of these findings is unclear but it is unlikely that these proteins, which are present only in small amounts, are major determinants of the plasma protein binding of basic drugs.…”

Overlapping Ligand Specificity of P-Glycoprotein and Serum α1-Acid Glycoprotein:Evidences and Potential Implications

“…According to the overlapping ligand specificity of AGP and P-gp, significant binding interaction is suggested between AGP and the substances listed in Table 4 [39,41,43,46,51,91,122,123,125,142,152,154,160,162,165,170,172,193,204,208,210,219,249,263,269,272,286,288,293,294,297,298,. According to the overlapping ligand specificity of AGP and P-gp, significant binding interaction is suggested between AGP and the substances listed in Table 4 [39,41,43,46,51,91,122,123,125,142,152,154,160,162,…”

Displacement of Disopyramide from Human Plasma Proteins

“…The results of table 2 and 3 thus indicate that the two substances are not bound to the same binding sites. Similarly timegadine (a basic non-steroidal antiinflammatory drug) is well displaced by quinidine, but not very well by disopyramide (George et a/. 1984).…”