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: Pharmacokinetic modeling of the dosing interval dependency for the interaction between itraconazole and triazolam.
    Author: Toi A, Ohtani H, Tsujimoto M, Sawada Y.
    Journal: Int J Clin Pharmacol Ther; 2010 Jun; 48(6):356-66. PubMed ID: 20497744.
    Abstract:
    OBJECTIVE: Itraconazole is a potent inhibitor of cytochrome P450 (CYP) 3A with an elimination half-life of more than 30 hours. Therefore, itraconazole may cause persistent CYP3A inhibition. Triazolam is primarily metabolized by CYP3A and its plasma concentration is increased remarkably by itraconazole. Although separating their dosages by 24 hours has been shown to reduce the interaction, an appropriate dosage interval remains to be determined. The aim of this study was to identify an appropriate dosage schedule to avoid their interaction. MATERIALS AND METHODS: We developed a pharmacokinetic model based on the assumption that both itraconazole and hydroxyitraconazole competitively and reversibly inhibit the first-pass metabolism and systemic elimination of triazolam. The developed model was simultaneously fitted to the plasma concentration profiles of triazolam, taken from the literature, by using the plasma concentration-time profiles of itraconazole and hydroxyitraconazole as input functions to estimate their in vivo Ki values. Subsequently, we simulated the plasma concentration profiles of triazolam administered after itraconazole therapy with various dosing intervals. RESULTS: The model could explain and simulate the interaction between itraconazole-triazolam using a variety of dosage intervals between the administrations. CONCLUSIONS: The developed model may provide useful information with regard to the appropriate interval for triazolam administration during itraconazole therapy.
    [Abstract] [Full Text] [Related] [New Search]