Trial reportBritish journal of clinical pharmacology2019
Simultaneous phenotyping of CYP2E1 and CYP3A using oral chlorzoxazone and midazolam microdoses.
Trial report in British journal of clinical pharmacology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT05257447 (Pharmacokinetic and Bioequivalence Comparison of Baclofen and Chlorzoxazone When Administered Individually or Concurrently), which is not on this map. Cited by 12 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.
Pharmacokinetic and Bioequivalence Comparison of Baclofen and Chlorzoxazone When Administered Individually or Concurrently
Who cites it
12 citing papers in PubMed, 20 citations in OpenAlex.
- Simultaneous phenotyping of CYP2E1 and CYP3A using oral chlorzoxazone and midazolam microdoses.British journal of clinical pharmacology · 2019Trial
- Challenging the specificity of chlorzoxazone and 4-nitrophenol as marker substrates for CYP2E1 activity in Supersomes™.Archives of toxicology · 2026Article
- Therapeutic efficacy of the BKCa channel opener chlorzoxazone in a mouse model of Fragile X syndrome.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 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
- Physiologically Based Pharmacokinetic (PBPK) Model Predictions of Disease Mediated Changes in Drug Disposition in Patients with Nonalcoholic Fatty Liver Disease (NAFLD).Pharmaceutical research · 2024Article
- One-Step Preparation of Fiber-Based Chlorzoxazone Solid Dispersion by Centrifugal Spinning.Polymers · 2023Article
- CYP3A and CYP2C19 Activity Determined by Microdosed Probe Drugs Accurately Predict Voriconazole Clearance in Healthy Adults.Clinical pharmacokinetics · 2023Article
- Physiologically Based Pharmacokinetic Modelling to Identify Physiological and Drug Parameters Driving Pharmacokinetics in Obese Individuals.Clinical pharmacokinetics · 2023Article
- Review
- Sensitive UHPLC-MS/MS quantification method for 4β- and 4α-hydroxycholesterol in plasma for accurate CYP3A phenotyping.Journal of lipid research · 2022Article
- Screening and identification of potential biomarkers and therapeutic drugs in melanoma via integrated bioinformatics analysis.Investigational new drugs · 2021Article
- Phase 0/microdosing approaches: time for mainstream application in drug development?Nature reviews. Drug discovery · 2020Review
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
aimsChlorzoxazone is the paradigm marker substrate for CYP2E1 phenotyping in vivo. Because at the commonly used milligram doses (250-750 mg) chlorzoxazone acts as an inhibitor of the CYP3A4/5 marker substrate midazolam, previous attempts failed to combine both drugs in a common phenotyping cocktail. Microdosing chlorzoxazone could circumvent this problem.
methodWe enrolled 12 healthy volunteers in a trial investigating the dose-exposure relationship of single ascending chlorzoxazone oral doses over a 10,000-fold range (0.05-500 mg) and assessed the effect of 0.1 and 500 mg of chlorzoxazone on oral midazolam pharmacokinetics (0.003 mg).
resultsChlorzoxazone area under the concentration-time curve was dose-linear in the dose range between 0.05 and 5 mg. A nonlinear increase occurred with doses ≥50 mg, probably due to saturated presystemic metabolic elimination. While midazolam area under the concentration-time curve increased 2-fold when coadministered with 500 mg of chlorzoxazone, there was no pharmacokinetic interaction between chlorzoxazone and midazolam microdoses.
conclusionThe chlorzoxazone microdose did not interact with the CYP3A marker substrate midazolam, enabling the simultaneous administration in a phenotyping cocktail. This microdose assay is now ready to be further validated and tested as a phenotyping procedure assessing the impact of induction and inhibition of CYP2E1 on chlorzoxazone microdose pharmacokinetics.
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