Pharmacokinetics of desogestrel

Abstract

A synthetic form of desogestrel, a gonane progestin, was developed because desogestrel's enhanced selectivity eliminates adverse, androgen-dependent, metabolic effects at contraceptive doses. Desogestrel is rapidly and completely metabolized in the liver and gut wall to 3-keto-desogestrel, which is the active metabolite mediating the progestin effects. Because of its unique 11-methylene side chain, desogestrel cannot be metabolized to any other known progestin, nor is desogestrel a naturally occurring metabolite of any other progestin. The pharmacokinetic parameters of 3-keto-desogestrel are generally comparable with those of levonorgestrel and norethindrone. Therefore any differences in pharmacologic activities must be attributed to differences in intrinsic activities. Unlike gestodene, 3-keto-desogestrel has a lower affinity for sex hormone-binding globulin, which results in markedly lower plasma levels after administration. After oral administration of 150 micrograms of desogestrel, plasma levels are less than half the levels of gestodene after an oral dose of 75 micrograms.