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Ketoconazole Blocks Adrenal Steroid Synthesis
Abstract
Ketoconazole, a broad-spectrum, antifungal drug that is administered orally, has been shown to inhibit sterol synthesis in fungi. When gynecomastia developed in some patients taking this drug, we investigated the effects of ketoconazole on steroid synthesis in humans and in isolated adrenal cells from rats. In healthy humans, the cortisol response to adrenocorticotropic hormone was significantly blunted 4 hours after a 400-mg or 600-mg dose. The inhibition persisted for up to 8 hours and was absent by 16 hours. This finding indicated that adrenal androgen response was reduced. Easily achieved therapeutic concentrations of ketoconazole virtually eliminated corticosterone production by isolated adrenal cells from rats. Although ketoconazole at currently used doses has never been documented to cause clinical hypoadrenalism, caution is urged in high- or multiple-dose trials. The drug may prove useful as an agent to block steroid synthesis.
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Citations
Cited by
A history of prostate cancer treatment.
Denmeade, S. R., & Isaacs, J. T. (2002) · Nature reviews. Cancer · doi:10.1038/nrc801 · Cited by 591
Inhibition of Adrenal Steroidogenesis by the Anesthetic Etomidate
Wagner, R. L., White, P. F., Kan, P. B., Rosenthal, M. H., & Feldman, D. (1984) · New England Journal of Medicine · doi:10.1056/nejm198405313102202 · Cited by 555
Self-citationAzole antifungal agents: Emphasis on new triazoles
Saag, M. S., & Dismukes, W. E. (1988) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.32.1.1 · Cited by 474
Overview of medically important antifungal azole derivatives
Fromtling, R. A. (1988) · Clinical Microbiology Reviews · doi:10.1128/cmr.1.2.187 · Cited by 398
The use of ketoconazole as an inhibitor of steroid production
Oates, J. A., Wood, A. J. J., & Sonino, N. (1987) · New England Journal of Medicine · doi:10.1056/nejm198709243171307 · Cited by 395
Metadata
- Authors
- PONT, A., WILLIAMS, P. L., LOOSE, D. S., FELDMAN, D., REITZ, R. E., BOCHRA, C., & STEVENS, D. A.
- Venue
- Annals of Internal Medicine
- Publisher
- American College of Physicians
- Published
- 1982-09-01
- Volume
- 97
- Issue
- 3
- Pages
- 370-372
- ISSN
- 0003-4819 (ISSN-L)
- 1539-3704
- OpenAlex
- W1990893435
- Cited by
- 422
- References
- 0
- FWCI
- 25.51
- Type
- journal article
- Language
- en
- Open access
- closed
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- The paper
- PONT, A., WILLIAMS, P. L., LOOSE, D. S., FELDMAN, D., REITZ, R. E., BOCHRA, C., & STEVENS, D. A. (1982). Ketoconazole Blocks Adrenal Steroid Synthesis. Annals of Internal Medicine. https://doi.org/10.7326/0003-4819-97-3-370
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
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