Aromatase inhibition by the antifungal ketoconazole.
The aromatase inhibitory properties of the antifungal ketoconazole were compared with those of aminoglutethimide. In rat granulosa cells ketoconazole and aminoglutethimide showed IC50 values for aromatase inhibition of 2 X 10(-6) and 6 X 10(-7) M respectively. In the rat, in vivo, ketoconazole was 5 times less potent than aminoglutethimide. In young women, 400 mg of ketoconazole only marginally lowered plasma levels of estradiol-17 beta. It is concluded that ketoconazole is not a compound of choice for clinical use as an aromatase inhibitor.
Wouters
W
W
Department of Life Sciences, Janssen Pharmaceutica, Beerse, Belgium.
De Coster
R
R
Goeminne
N
N
Beerens
D
D
van Dun
J
J
D000328:Adult; D000616:Aminoglutethimide / Q000494:pharmacology; D000818:Animals; D047072:Aromatase Inhibitors; D002478:Cells, Cultured; D004958:Estradiol / Q000097:blood*; D005260:Female; D005498:Follicular Phase / Q000187:drug effects; D006107:Granulosa Cells / Q000201:enzymology*; D006801:Humans; D007654:Ketoconazole / Q000494:pharmacology*; D007700:Kinetics; D008183:Luteal Phase / Q000187:drug effects; D051381:Rats; D011919:Rats, Inbred Strains
D047072:Aromatase Inhibitors; D000616:Aminoglutethimide; D004958:Estradiol; D007654:Ketoconazole