PMID: 12489563Dec 20, 2002Paper

Assessing pregnancy risks of azole antifungals using a high throughput aromatase inhibition assay

Endocrine Research
Laura KragieDavid M Stresser

Abstract

Human aromatase (CYP19) converts C19 androgens to aromatic C18 estrogenic steroids. Its activity is critical for early and mid pregnancy maintenance and in regulating parturition in late pregnancy. Past studies have utilized placental microsome tritiated water release assay to assess drug-hormone interactions with estrogen synthesis. We compared data from human placental assays with BD Gentest's high throughput recombinant CYP19 enzyme assay using the fluorometric substrate dibenzylfluorescein. We tested a panel of azole antifungal agents that are commonly administered to women of childbearing potential, for their potential to inhibit aromatase. Potency varied by several orders of magnitude. Plasma and tissue levels of some azole drugs following oral or topical administration are at or above these IC50 values. These include the oral agents fluconazole and ketoconazole, and the topical agents econazole, bifonazole, clotrimazole, miconazole, and sulconazole. 1. Recombinant enzyme assay data are comparable to the human placental assay data in both SAR rank order and potency. 2. Plasma and tissue levels of some azole drugs following oral or topical administration are at or above these IC50 values. Therefore, some azole drugs may di...Continue Reading

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Citations

Dec 20, 2002·Endocrine Research·Laura Kragie
Jun 13, 2009·Pharmaceutical Development and Technology·Mukesh C Gohel, Stavan A Nagori
Aug 7, 2013·Dermatologic Therapy·Carly A Elston, Dirk M Elston
Apr 28, 2017·Journal of the European Academy of Dermatology and Venereology : JEADV·V M PatelW C Lambert
Dec 17, 2009·Birth Defects Research. Part A, Clinical and Molecular Teratology·Nehama LinderPaul Merlob
Apr 29, 2020·Deutsches Ärzteblatt International·Philipp Conradi

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