ArticleClinical pharmacokinetics2012
Predicting drug candidate victims of drug-drug interactions, using microdosing.
Article in Clinical pharmacokinetics, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
What it found
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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.
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Who cites it
19 citing papers in PubMed, 42 citations in OpenAlex.
- Simultaneous phenotyping of CYP2E1 and CYP3A using oral chlorzoxazone and midazolam microdoses.British journal of clinical pharmacology · 2019Trial
- Drug-drug interaction of microdose and regular-dose omeprazole with a CYP2C19 inhibitor and inducer.Drug design, development and therapy · 2017Trial
- The Effect of Ecopipam on the Pharmacokinetics of Concomitant Medications.Clinical and translational science · 2026Article
- Efavirenz and CYP2C9 Genetic Polymorphisms Reduce CYP2C9 Activity in Healthy Participants.Clinical and translational science · 2026Article
- Clinical Pharmacokinetics of Fexofenadine: A Systematic Review.Pharmaceutics · 2024Review
- 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
- The application of Phase 0 and microtracer approaches in early clinical development: past, present, and future.Frontiers in pharmacology · 2024Review
- Phase 0/microdosing approaches: time for mainstream application in drug development?Nature reviews. Drug discovery · 2020Review
- Predictive Value of Microdose Pharmacokinetics.Clinical pharmacokinetics · 2019Review
- Intra-Target Microdosing (ITM): A Novel Drug Development Approach Aimed at Enabling Safer and Earlier Translation of Biological Insights Into Human Testing.Clinical and translational science · 2017Review
- Microdosing and Other Phase 0 Clinical Trials: Facilitating Translation in Drug Development.Clinical and translational science · 2016Review
- To Apply Microdosing or Not? Recommendations to Single Out Compounds with Non-Linear Pharmacokinetics.Clinical pharmacokinetics · 2016Article
- Intraarterial Microdosing: A Novel Drug Development Approach, Proof-of-Concept PET Study in Rats.Journal of nuclear medicine : official publication, Society of Nuclear Medicine · 2015Article
- Single cell measurement of telomerase expression and splicing using microfluidic emulsion cultures.Nucleic acids research · 2015Article
- Use of microdose phenotyping to individualise dosing of patients.Clinical pharmacokinetics · 2015Article
- Proximal Roux-en-Y gastric bypass alters drug absorption pattern but not systemic exposure of CYP3A4 and P-glycoprotein substrates.Pharmacotherapy · 2015Article
- Midazolam microdose to determine systemic and pre-systemic metabolic CYP3A activity in humans.British journal of clinical pharmacology · 2015Article
- Geneva cocktail for cytochrome p450 and P-glycoprotein activity assessment using dried blood spots.Clinical pharmacology and therapeutics · 2014Article
- Microdosing and drug development: past, present and future.Expert opinion on drug metabolism & toxicology · 2013Review
Corrections and comments
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Authors and funding
5 authors at 3 institutions in 2 countries.
Funding
Abstract
objectiveThe aim of this crossover human male volunteer study was to investigate the utility of microdosing in the investigation of drug-drug interactions.
methodsA mixture of midazolam, tolbutamide, caffeine and fexofenadine were administered as a microdose (25 μg each) before and after administration of a combined pharmacological dose of ketoconazole (400 mg) and fluvoxamine (100 mg) to inhibit P-glycoprotein and metabolism by cytochrome P450 (CYP) 1A2, CYP3A4 and CYP2C9.
resultsWhen administered alone, pharmacokinetics for all four microdosed compounds scaled well with those reported for therapeutic doses and with previously performed microdose studies. The pharmacokinetics of each compound administered as a microdose were significantly altered after the administration of ketoconazole and fluvoxamine, showing statistically significant (p < 0.01) 12.8-, 8.1- and 3.2-fold increases in the area under the plasma concentration-time curve from time zero to infinity (AUC(∞)) for midazolam, caffeine and fexofenadine, respectively. A 1.8-fold increase (not statistically significant) in AUC(∞) was observed for tolbutamide. The changes in pharmacokinetics mediated by ketoconazole and fluvoxamine were quantitatively consistent with previously reported, non-microdose, drug-drug interaction data from studies including the same compounds.
conclusionThe initial data reported here demonstrate the utility of microdosing to investigate the risk of development drugs being victims of drug-drug interactions.
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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.