[The endocrinologic profile of metabolites of the progestin dienogest].
Two identified metabolites of the orally active progestin dienogest, the compounds STS 749 (17 alpha-cyanomethyl-11 beta,17 beta-dihydroxy-estra-4,9-dien-3-one) and STS 825 (17 alpha-cyanomethyl-estra-1,3,5(10),9(11)-tetraene-3,17 beta-diol), furthermore 4 microbially formed metabolites and 10 chemically prepared analoga of dienogest were characterized by endocrinological tests. The compounds were investigated for progesterone-receptor binding, progestational and antiprogestational, estrogenic and antigonadotropic activities, furthermore for inhibition of fertility. In no case an increased progestational activity of metabolites or analoga was found, compared to the parent substance. Therefore, it should be excluded, that dienogest acts as a prodrug. Additionally, the dosages necessary to produce the progestational effects are quite similar using oral or subcutaneous application. Therefore, a first-pass effect can be neglected. Regarding the low endocrine side effects of dienogest, the antiprogestational activity may be caused, at least in part, by metabolites.
Oettel
M
M
JENAPHARM GmbH, Jena.
Kaufmann
G
G
Kurischko
A
A
D000726:Androgen Antagonists / Q000494:pharmacology; D000818:Animals; D004717:Endometrium / Q000187:drug effects; D045166:Estradiol Congeners / Q000494:pharmacology; D005260:Female; D005298:Fertility / Q000187:drug effects; D066298:In Vitro Techniques; D008297:Male; D051379:Mice; D009277:Nandrolone / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology; D011247:Pregnancy; D011372:Progestins / Q000378:metabolism / Q000494:pharmacology*; D011817:Rabbits; D051381:Rats; D017208:Rats, Wistar; D011980:Receptors, Progesterone / Q000187:drug effects / Q000378:metabolism
D000726:Androgen Antagonists; D045166:Estradiol Congeners; D011372:Progestins; D011980:Receptors, Progesterone; C023635:dienogest; D009277:Nandrolone