The plasma protein binding and distribution of etomidate in dog, rat and human blood
Meuldermans, W.E.; Heykants, J.J.
Archives Internationales de Pharmacodynamie et de Therapie 221(1): 150-162
1976
ISSN/ISBN: 0003-9780 PMID: 962425 Document Number: 99686
The interactions of etomidate and its major metabolite [1-(1-phenylethyl)-1H-imidazole-5-carboxylic acid] (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 28 141, 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, the etomidate was partly hydrolyzed, even in the presence of NaF. 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.