title: The plasma protein binding and distribution of etomidate in dog, rat and human blood.
abstract: The interactions of etomidate and its major metabolite  (R 28 141) with plasma proteins were studied by equilibrium dialysis with a multiple cell system. A 4% human serum albumin solution was able to bind 78.5% of the etomidate, and 60.5% of R 25 141, whereas a 1.5% human gamma globulin solution bound etomidate for not more than 3% and did not bind R 28 141 at all. The association constants and free binding energies for the binding of etomidate and R 28 141 to human serum albumin were determined. Plasma protein binding of etomidate was 75.4% in the dog and 76.5% in man; in rat plasma 79.5% of the radioactivity was bound to the plasma proteins, however the etomidate was partly hydrolyzed, even in the presence of sodium fluoride. In the rat 29.7% was distributed to the blood cells, 55.9% bound to plasma proteins and 14.4% was present in plasma water; in the dog the distribution percentages were 42.1%, 43.7% and 14.2% respectively, and in man 37.7%, 47.6% and 14.7% respectively. The major metabolite of etomidate was distributed for 26.3% to the human blood cells, 47.4% was bound to plasma proteins and 26.2% was present in the plasma water; its plasma protein binding amounted to 64.3%. Etomidate was bound at or in the blood cells, whereas R 28 141 was not.
mesh_terms: D001798:Blood Proteins / Q000378:metabolism*; D002850:Chromatography, Gel; D003956:Dialysis; D005260:Female; D006801:Humans; D007093:Imidazoles / Q000097:blood*; D066298:In Vitro Techniques; D008297:Male; D011485:Protein Binding; D012710:Serum Albumin, Bovine / Q000378:metabolism; D014461:Ultracentrifugation
chemical_list: D001798:Blood Proteins; D007093:Imidazoles; D012710:Serum Albumin, Bovine