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Cytochrome p‐450: Target for itraconazole
Author(s) -
Vanden Bossche Hugo,
Bellens Dany,
Cools Willy,
Gorrens Jos,
Marichal Patrick,
Verhoeven Hugo,
Willemsens Gustaaf,
De Coster Roland,
Beerens Dominiek,
Haelterman Christian,
Coene MarieClaire,
Lauwers William,
le Jeune Ludo
Publication year - 1986
Publication title -
drug development research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.582
H-Index - 60
eISSN - 1098-2299
pISSN - 0272-4391
DOI - 10.1002/ddr.430080133
Subject(s) - lanosterol , ketoconazole , itraconazole , demethylation , chemistry , cytochrome , cyp3a4 , ergosterol , candida albicans , hydroxylation , miconazole , cytochrome p450 , microsome , biochemistry , pharmacology , medicine , in vitro , biology , metabolism , cholesterol , sterol , enzyme , microbiology and biotechnology , antifungal , gene expression , gene , dna methylation
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.