Binding in vitro of pipequaline (45319 RP) onto plasma proteins and blood cells in man.
Serum binding of pipequaline, a new anxiolytic drug, was studied in vitro by equilibrium dialysis. The percent binding in serum is high, 96.3%, and remains constant within the range of therapeutic concentrations. Investigations performed on isolated proteins with a wide range of concentrations showed one site with a high affinity constant (Ka = 450,000 M-1) for alpha 1-acid glycoprotein and two sites with a lower affinity constant (Ka = 58,000 M-1) for human serum albumin. Binding to lipoproteins was saturable, with an affinity constant of 22,000 less than or equal to Ka less than or equal to 35,000 M-1. Over the range of therapeutic concentrations, the ratio of pipequaline concentrations in serum and red blood cells remained constant (14.4%) and was shown to be dependent on the free fraction of pipequaline in serum.
D000328:Adult; D014151:Anti-Anxiety Agents / Q000378:metabolism*; D001773:Blood Cells / Q000378:metabolism*; D001798:Blood Proteins / Q000378:metabolism*; D003975:Diazepam / Q000494:pharmacology; D004912:Erythrocytes / Q000378:metabolism; D005230:Fatty Acids, Nonesterified / Q000378:metabolism; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D008074:Lipoproteins / Q000378:metabolism; D008297:Male; D011485:Protein Binding; D011804:Quinolines / Q000378:metabolism*; D012709:Serum Albumin / Q000378:metabolism; D014018:Tissue Distribution; D014859:Warfarin / Q000494:pharmacology
D014151:Anti-Anxiety Agents; D001798:Blood Proteins; D005230:Fatty Acids, Nonesterified; D008074:Lipoproteins; D011804:Quinolines; D012709:Serum Albumin; D014859:Warfarin; C030078:pipequaline; D003975:Diazepam