Trial reportClinical pharmacology and therapeutics2008
Contribution of itraconazole metabolites to inhibition of CYP3A4 in vivo.
Trial report in Clinical pharmacology and therapeutics, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
46 citing papers in PubMed, 134 citations in OpenAlex.
- A semiphysiological population pharmacokinetic model for dynamic inhibition of liver and gut wall cytochrome P450 3A by voriconazole.Clinical pharmacokinetics · 2013Trial
- Effect of itraconazole on the concentrations of tacrolimus and cyclosporine in the blood of patients receiving allogeneic hematopoietic stem cell transplants.European journal of clinical pharmacology · 2013Trial
- CYP2C8 but not CYP3A4 is important in the pharmacokinetics of montelukast.British journal of clinical pharmacology · 2012Trial
- Accurate prediction of dose-dependent CYP3A4 inhibition by itraconazole and its metabolites from in vitro inhibition data.Clinical pharmacology and therapeutics · 2010Trial
- Berberine as a Promising Antifungal Agent: Insights into Molecular Mechanisms and Therapeutic Potential.ACS omega · 2026Review
- Role of metabolites in drug-drug interactions.Drug metabolism and pharmacokinetics · 2026Review
- Therapeutic drug monitoring of itraconazole in treatment of blastomycosis in dogs.Journal of veterinary internal medicine · 2026Article
- The strong clinical interaction between bupropion and CYP2D6 is primarily mediated through bupropion metabolites and their stereoisomers: A paradigm for evaluating metabolites in drug-drug interaction risk.Drug metabolism and disposition: the biological fate of chemicals · 2025Article
- Article
- Current Updates on Pathogenesis, Systemic Therapy, and Treatment of Invasive Fungal Infections.Current drug targets · 2025Review
- Understanding the mechanisms of food effect on omaveloxolone pharmacokinetics through physiologically based biopharmaceutics modeling.CPT: pharmacometrics & systems pharmacology · 2024Article
- Effects of Itraconazole on Pharmacokinetics of Mitragynine and 7-Hydroxymitragynine in Healthy Volunteers.ACS pharmacology & translational science · 2024Article
- Evaluation of drug-drug interaction between Suraxavir Marboxil (GP681) and itraconazole, and assessment of the impact of gene polymorphism.Frontiers in pharmacology · 2024Article
- Evaluation of the Potential for Drug-Drug Interactions with Inhaled Itraconazole Using Physiologically Based Pharmacokinetic Modelling, Based on Phase 1 Clinical Data.The AAPS journal · 2023Article
- Itraconazole-Induced Increases in Gilteritinib Exposure Are Mediated by CYP3A and OATP1B.Molecules (Basel, Switzerland) · 2022Article
- Interaction of Antifungal Drugs with CYP3A- and OATP1B-Mediated Venetoclax Elimination.Pharmaceutics · 2022Article
- Model-based assessments of CYP3A-mediated drug-drug interaction risk of milademetan.Clinical and translational science · 2021Article
- Do Inhibitory Metabolites Impact DDI Risk Assessment? Analysis of in vitro and in vivo Data from NDA Reviews Between 2013 and 2018.Clinical pharmacology and therapeutics · 2021Article
- Multienzyme Kinetics and Sequential Metabolism.Methods in molecular biology (Clifton, N.J.) · 2021Article
- How Science Is Driving Regulatory Guidances.Methods in molecular biology (Clifton, N.J.) · 2021Article
Corrections and comments
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
Itraconazole (ITZ) is metabolized in vitro to three inhibitory metabolites: hydroxy-itraconazole (OH-ITZ), keto-itraconazole (keto-ITZ), and N-desalkyl-itraconazole (ND-ITZ). The goal of this study was to determine the contribution of these metabolites to drug-drug interactions caused by ITZ. Six healthy volunteers received 100 mg ITZ orally for 7 days, and pharmacokinetic analysis was conducted at days 1 and 7 of the study. The extent of CYP3A4 inhibition by ITZ and its metabolites was predicted using this data. ITZ, OH-ITZ, keto-ITZ, and ND-ITZ were detected in plasma samples of all volunteers. A 3.9-fold decrease in the hepatic intrinsic clearance of a CYP3A4 substrate was predicted using the average unbound steady-state concentrations (C(ss,ave,u)) and liver microsomal inhibition constants for ITZ, OH-ITZ, keto-ITZ, and ND-ITZ. Accounting for circulating metabolites of ITZ significantly improved the in vitro to in vivo extrapolation of CYP3A4 inhibition compared to a consideration of ITZ exposure alone.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.