[Effect of non-steroidal anti-inflammatory drugs on plasma protein binding of corticosterones (author's transl)]

Abstract

A series of non-steroid antiinflammatory drugs (NSAD) as well as substances with different spectra of pharmacological action were investigated with regard to the influence on binding of corticosterone to plasma protein in rats after repeated oral administration. At pharmacologically active doses, NSAD cause a time and dose dependent increase in rat plasma of the corticosterone fraction which can be ultra-filtrated. The effect on corticosterone binding to plasma protein largely parallels the antiinflammatory efficacy of the NSAD. This does not occur by a mere displacement of corticosterone from the plasma protein binding, but is apparently the consequence of a qualitative and/or quantitative change of the binding proteins. Organic acids, cytostatic or other drugs which strongly bind to plasma protein do not show any corresponding influence on the corticosterone binding to plasma protein under comparable conditions. The increase of the fraction of corticosterone which can be ultra-filtrated effected by the NSAD accelerates the excretion of corticosterone into the bile of rats. The phenomenon of decrease in binding of corticosteroids to plasma protein is discussed with respect to its importance for the mode of action of the NSAD.