Trial reportClinical pharmacology and therapeutics2010
Accurate prediction of dose-dependent CYP3A4 inhibition by itraconazole and its metabolites from in vitro inhibition data.
Trial report in Clinical pharmacology and therapeutics, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 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
33 citing papers in PubMed, 68 citations in OpenAlex.
- Siponimod pharmacokinetics, safety, and tolerability in combination with the potent CYP3A4 inhibitor itraconazole in healthy subjects with different CYP2C9 genotypes.European journal of clinical pharmacology · 2019Trial
- Does In Vitro Cytochrome P450 Downregulation Translate to In Vivo Drug-Drug Interactions? Preclinical and Clinical Studies With 13-cis-Retinoic Acid.Clinical and translational science · 2019Trial
- Effects of cytochrome P450 (CYP3A4 and CYP2C19) inhibition and induction on the exposure of selumetinib, a MEK1/2 inhibitor, in healthy subjects: results from two clinical trials.European journal of clinical pharmacology · 2017Trial
- An S-warfarin and AZD1981 interaction: in vitro and clinical pilot data suggest the N-deacetylated amino acid metabolite as the primary perpetrator.British journal of clinical pharmacology · 2017Trial
- Proteomic and functional profiling of suspended jejunal enteroids reveals pharmacokinetic fidelity to native intestine.iScience · 2026Article
- Repurposing Non-oncologic Drugs via Targeted Nanocarriers for Cancer Therapy: Mechanisms, Synergistic Combinations, and Clinical Translation.AAPS PharmSciTech · 2026Review
- Limitations of Subgroup Safety Analyses for Drug-Drug Interaction Evaluation: Insights from the Talazoparib P-gp Inhibitor Case.Journal of clinical pharmacology · 2026Article
- Role of metabolites in drug-drug interactions.Drug metabolism and pharmacokinetics · 2026Review
- Endocrine consequences of antifungal therapy: A missed entity.World journal of clinical cases · 2026Review
- Drug Interaction Between Erlotinib and Itraconazole in a Patient With Non-Small Cell Lung Cancer.Case reports in oncological medicine · 2026Article
- Trends in drug-drug interactions for new drug clinical trials in China over the past 10 years (2013-2022).BMC pharmacology & toxicology · 2025Article
- Understanding the mechanisms of food effect on omaveloxolone pharmacokinetics through physiologically based biopharmaceutics modeling.CPT: pharmacometrics & systems pharmacology · 2024Article
- The Use of Microdosing for In vivo Phenotyping of Cytochrome P450 Enzymes: Where Do We Stand? A Narrative Review.European journal of drug metabolism and pharmacokinetics · 2024Review
- 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
- Repurposing antifungal drugs for cancer therapy.Journal of advanced research · 2023Review
- Evaluation of the effects of four types of tea on the activity of cytochrome P450 enzymes with a probe cocktail and HPLC-MS/MS.Annals of translational medicine · 2022Article
- Recommendations for the Design of Clinical Drug-Drug Interaction Studies With Itraconazole Using a Mechanistic Physiologically-Based Pharmacokinetic Model.CPT: pharmacometrics & systems pharmacology · 2019Article
- Impact of Lipid Partitioning on the Design, Analysis, and Interpretation of Microsomal Time-Dependent Inactivation.Drug metabolism and disposition: the biological fate of chemicals · 2019Article
- Article
- PBPK Models for CYP3A4 and P-gp DDI Prediction: A Modeling Network of Rifampicin, Itraconazole, Clarithromycin, Midazolam, Alfentanil, and Digoxin.CPT: pharmacometrics & systems pharmacology · 2018Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
Inhibitory drug metabolites may contribute to drug-drug interactions (DDIs). The aim of this study was to determine the importance of inhibitory metabolites of itraconazole (ITZ) in in vivo cytochrome P450 (CYP) 3A4 inhibition. The pharmacokinetics of ITZ and midazolam (MDZ) were determined in six healthy volunteers in four sessions after administration of MDZ with and without oral ITZ. After doses of 50, 200, and 400 mg of ITZ, the clearance of orally administered MDZ decreased by 27, 74, and 83%, respectively. The in vivo half maximal inhibitory concentration (IC(50)) for ITZ ranged from 5 to 132 nmol/l in the six subjects. The metabolites of ITZ were estimated to account for ~50% of the total CYP3A4 inhibition, with the relative contribution increasing with time after ITZ dosing. Of the total of 18 interactions observed, 15 (84%) could be predicted within a twofold error margin, with improved accuracy observed when ITZ metabolites were included in the predictions. This study shows that the metabolites of ITZ contribute to CYP3A4 inhibition and need to be accounted for in quantitative rationalization of ITZ-mediated DDIs.
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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.