Cytochrome p‐450: Target for itraconazole

• Hugo Vanden Bossche

• Dany Bellens

• Willy Cools

• Jos Gorrens

• Patrick Marichal

• Hugo Verhoeven

• Gustaaf Willemsens

• Roland De Coster

• Dominiek Beerens

• Christian Haelterman

• Marie‐Claire Coene

• William Lauwers

• Ludo le Jeune

抄録

The N ‐substituted triazole, itraconazole, has high affinity for the cytochrome P‐450 (cyt. P‐450) isozyme involved in the 14α‐demethylation of lanosterol in Candida albicans microsomes. Fifty per cent inhibition was already observed at itraconazole concentrations ≤ 5 × 10 −9 M. Higher concentrations (≥ 10 −7 M) of this antifungal are needed to interfere with the 14 α‐demethylation in mammalian cells. Unlike ketoconazole, itraconazole does not significantly affect in vitro androgen, gluco‐ and mineralocorticoid steroidogenesis. Itraconazole also does not affect the cyt. P‐450‐dependent 19‐hydroxylation of testosterone, a step in the conversion of androgens to estrogens. The 1‐hydroxylation of testosterone by pig testes microscomes is only slightly inhibited. It is hypothesized that itraconazole's selective activity on ergosterol bisosynthesis is due to its high affinity for the apoprotein of the C. albicans cyt. P‐450 involved in the 14α‐ demethylation of lanosterol.

収録刊行物

• Drug Development Research

  Drug Development Research 8 (1-4), 287-298, 1986-05

  Wiley

キーワード

• Drug Discovery

詳細情報

• CRID: 1361418519587422976
• NII論文ID: 30011647518
• NII書誌ID: AA10654891
• DOI: 10.1002/ddr.430080133
• ISSN: 10982299
• ISSN: 02724391
• Web Site: https://api.wiley.com/onlinelibrary/tdm/v1/articles/10.1002%2Fddr.430080133
• Web Site: https://onlinelibrary.wiley.com/doi/pdf/10.1002/ddr.430080133
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