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• W2049689240 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. Conclusions: 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 disrupt estrogen production in pregnancy, affecting pregnancy outcome. 3. Recombinant CYP19 assay using the fluorometric substrate dibenzylfluorescein, demonstrates rapid screening potential for chemicals that may affect pregnancy outcome as a result of CYP19 inhibition." @default.
• W2049689240 created "2016-06-24" @default.
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• W2049689240 date "2002-01-01" @default.
• W2049689240 modified "2023-10-18" @default.
• W2049689240 title "ASSESSING PREGNANCY RISKS OF AZOLE ANTIFUNGALS USING A HIGH THROUGHPUT AROMATASE INHIBITION ASSAY" @default.
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• W2049689240 doi "https://doi.org/10.1081/erc-120015045" @default.
• W2049689240 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/12489563" @default.
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