Plasma levels of levonorgestrel, gestodene, norethisterone and cyproterone acetate on single-dose subcutaneous administration in oily solution in the rat, beagle and rhesus monkey.

This report describes the pharmacokinetics of levonorgestrel, gestodene, norethisterone and cyproterone acetate following subcutaneous administration of oily solutions in the rat, beagle dog and rhesus monkey. The plasma levels of the progestogens were measured by means of specific radioimmunoassays. Half-lives calculated for the disposition process of a particular metabolically unchanged drug in plasma revealed marked differences in different animal species. Furthermore, comparison of the different progestogens showed large variations in this parameter in all the animal species. It became obvious that there are physico-chemical properties as well as metabolic rate limitations effecting the release and elimination of synthetic progestogens administered in oily solution. The results are compared with the half-lives of these progestogens administered intravenously as reported previously. A prolongation of half-life as a result of the depot effect of subcutaneous administration was demonstrated for all the progestogens in the rat, the beagle dog and the rhesus monkey.