Trial reportEuropean journal of clinical pharmacology2004
Oral administration of a low dose of midazolam (75 microg) as an in vivo probe for CYP3A activity.
Trial report in European journal of clinical pharmacology, 2004. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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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
32 citing papers in PubMed, 95 citations in OpenAlex.
- Pharmacokinetic Drug-Drug Interaction of Apalutamide, Part 1: Clinical Studies in Healthy Men and Patients with Castration-Resistant Prostate Cancer.Clinical pharmacokinetics · 2020Trial
- Influence of Panax ginseng on cytochrome P450 (CYP)3A and P-glycoprotein (P-gp) activity in healthy participants.Journal of clinical pharmacology · 2012Trial
- The effects of CYP2D6 and CYP3A activities on the pharmacokinetics of immediate release oxycodone.British journal of pharmacology · 2010Trial
- Genetic polymorphisms and drug interactions modulating CYP2D6 and CYP3A activities have a major effect on oxycodone analgesic efficacy and safety.British journal of pharmacology · 2010Trial
- Inhibition of oral midazolam clearance by boosting doses of ritonavir, and by 4,4-dimethyl-benziso-(2H)-selenazine (ALT-2074), an experimental catalytic mimic of glutathione oxidase.British journal of clinical pharmacology · 2009Trial
- Pharmacokinetics of intravenous and oral midazolam in plasma and saliva in humans: usefulness of saliva as matrix for CYP3A phenotyping.British journal of clinical pharmacology · 2008Trial
- Alprazolam as a probe for CYP3A using a single blood sample: pharmacokinetics of parent drug, and of alpha- and 4-hydroxy metabolites in healthy subjects.European journal of clinical pharmacology · 2005Trial
- Variations of CYP3A activity induced by antiretroviral treatment in HIV-1 infected patients.European journal of clinical pharmacology · 2005Trial
- Pharmacokinetics of midazolam in CYP3A4- and CYP3A5-genotyped subjects.European journal of clinical pharmacology · 2004Trial
- Physiologically Based Pharmacokinetic Modeling to Predict Drug-Drug Interactions of Soticlestat as a Victim of CYP Induction and Inhibition, and as a Perpetrator of CYP and P-Glycoprotein Inhibition.Clinical pharmacology in drug development · 2025Article
- 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
- Pharmacokinetics and phenotyping properties of the Basel phenotyping cocktail combination capsule in healthy male adults.British journal of clinical pharmacology · 2020Article
- Inherited and Acquired Determinants of Hepatic CYP3A Activity in Humans.Frontiers in genetics · 2020Article
- Validation of a 3-h Sampling Interval to Assess Variability in Cytochrome P450 3A Phenotype and the Impact of Induction and Mechanism-Based Inhibition Using Midazolam as a Probe Substrate.Frontiers in pharmacology · 2019Article
- 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
- Analysis of Clinical Drug-Drug Interaction Data To Predict Magnitudes of Uncharacterized Interactions between Antiretroviral Drugs and Comedications.Antimicrobial agents and chemotherapy · 2018Article
- Physiologically Based Pharmacokinetic Model of the CYP2D6 Probe Atomoxetine: Extrapolation to Special Populations and Drug-Drug Interactions.Drug metabolism and disposition: the biological fate of chemicals · 2017Article
- Personalized prescribing: a new medical model for clinical implementation of psychotropic drugs.Dialogues in clinical neuroscience · 2016Review
- Prediction of Drug-Drug Interactions Arising from CYP3A induction Using a Physiologically Based Dynamic Model.Drug metabolism and disposition: the biological fate of chemicals · 2016Article
Corrections and comments
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Authors and funding
11 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
objectiveWe investigated whether the oral administration of a low dose (75 micro g) of midazolam, a CYP3A probe, can be used to measure the in vivo CYP3A activity.
methodsPlasma concentrations of midazolam, 1'OH-midazolam and 4'OH-midazolam were measured after the oral administration of 7.5 mg and 75 micro g midazolam in 13 healthy subjects without medication, in four subjects pretreated for 2 days with ketoconazole (200 mg b.i.d.), a CYP3A inhibitor, and in four subjects pretreated for 4 days with rifampicin (450 mg q.d.), a CYP3A inducer.
resultsAfter oral administration of 75 micro g midazolam, the 30-min total (unconjugated + conjugated) 1'OH-midazolam/midazolam ratios measured in the groups without co-medication, with ketoconazole and with rifampicin were (mean+/-SD): 6.23+/-2.61, 0.79+/-0.39 and 56.1+/-12.4, respectively. No side effects were reported by the subjects taking this low dose of midazolam. Good correlations were observed between the 30-min total 1'OH-midazolam/midazolam ratio and midazolam clearance in the group without co-medication (r(2)=0.64, P<0.001) and in the three groups taken together (r(2)=0.91, P<0.0001). Good correlations were also observed between midazolam plasma levels and midazolam clearance, measured between 1.5 h and 4 h.
conclusionA low oral dose of midazolam can be used to phenotype CYP3A, either by the determination of total 1'OH-midazolam/midazolam ratios at 30 min or by the determination of midazolam plasma levels between 1.5 h and 4 h after its administration.
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