warfarin and pipequaline

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.

Topics: Adult; Anti-Anxiety Agents; Blood Cells; Blood Proteins; Diazepam; Erythrocytes; Fatty Acids, Nonesterified; Female; Humans; In Vitro Techniques; Lipoproteins; Male; Protein Binding; Quinolines; Serum Albumin; Tissue Distribution; Warfarin