[Effect of estrogens on pharmacokinetics of phenazone and N-acetyl-p-aminophenol]

The aim of the paper was to determine the effect of estrogens on the pharmacokinetics of drugs. The experimental models were made up of female rabbits with bilaterally removed ovaries or those being given mestranol for a long time . N-acetyl-p-amino-phenol and phenazone were the model substances. The effect of surplus as well as deficiency of estrogens on the pharmacokinetics of drugs was ascertained. The surface area under the curve of paracetamol concentration changes was found to diminish after the bilateral removal of ovaries; there was a shortening of the half-life period for the elimination phase, and also an increase of the total clearance. The application of mestranol has made the mentioned parameters behave adversely. The bilateral ovariectomy has led to an increase in the surface area under the curve for phenazone concentration changes, elongation of its half-life period for the elimination phase, and the diminution of the total clearance. These parameters followed the course in a manner being inverse to that in animals receiving mestranol. It may be concluded that estrogens induce the microsomal system of oxidases with mixed function, and exert inhibitory action on enzymes mediating in reactions of coupling.