These tools will no longer be maintained as of December 31, 2024. Archived website can be found here. PubMed4Hh GitHub repository can be found here. Contact NLM Customer Service if you have questions.


Pubmed for Handhelds

PUBMED FOR HANDHELDS

Search MEDLINE/PubMed

  • Title: Azoles, allylamines and drug metabolism.
    Author: Back DJ, Tjia JF, Abel SM.
    Journal: Br J Dermatol; 1992 Feb; 126 Suppl 39():14-8. PubMed ID: 1311943.
    Abstract:
    Four antifungal drugs, the azoles ketoconazole, itraconazole and fluconazole, and the allylamine terbinafine, were studied for their effects on the metabolism of cyclosporin A (CyA) and cortisol by human liver microsomes in vitro (n = 3). Ketoconazole produced marked inhibition of CyA hydroxylase (to metabolites M17 and M1) with IC50 and Ki values of 0.24 +/- 0.01 and 0.022 +/- 0.004 microM, respectively. On the basis of the IC50, itraconazole was 10 times less potent (IC50 of 2.2 +/- 0.2 microM), and fluconazole and terbinafine were each above 100 microM. No kinetic parameters were calculated for terbinafine because of the lack of inhibitory effects. Ketoconazole was the most potent inhibitor of cortisol metabolism (to 6 beta-hydroxycortisol, IC50 = 0.6 microM). Itraconazole produced marked inhibition of cortisol metabolism (IC50 = 2.4 microM), but fluconazole and terbinafine had little effect. These data confirm that ketoconazole is a potent inhibitor of cytochrome P-450-IIIA4, and this has clinical relevance. Although the inhibition with fluconazole was much less than with itraconazole at equimolar concentrations, it should be noted that in-vivo plasma concentrations of fluconazole are much greater than that of itraconazole. Clinical interactions of CyA with both fluconazole and itraconazole have been reported; in contrast to these azoles, terbinafine does not have the same interaction potential.
    [Abstract] [Full Text] [Related] [New Search]