Trial reportEuropean journal of clinical pharmacology2006
Probe of CYP3A by a single-point blood measurement after oral administration of midazolam in healthy elderly volunteers.
Trial report in European journal of clinical pharmacology, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers, 1 of them a synthesis that pooled it.
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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
11 citing papers in PubMed, 1 synthesis or guideline pooled it, 19 citations in OpenAlex.
- Association of genotypes of the CYP3A cluster with midazolam disposition in vivo.The pharmacogenomics journal · 2009Pooled it
- Rate of onset of inhibition of gut-wall and hepatic CYP3A by clarithromycin.European journal of clinical pharmacology · 2013Trial
- Concurrent assessment of hepatic and intestinal cytochrome P450 3A activities using deuterated alfentanil.Clinical pharmacology and therapeutics · 2011Trial
- Prediction of Pharmacokinetics for CYP3A4-Metabolized Drugs in Pediatrics and Geriatrics Using Dynamic Age-Dependent Physiologically Based Pharmacokinetic Models.Pharmaceutics · 2025Article
- Evaluation of the Potential for Cytochrome P450 and Transporter-Mediated Drug-Drug Interactions for Firsocostat, a Liver-Targeted Inhibitor of Acetyl-CoA Carboxylase.Clinical pharmacokinetics · 2024Article
- Serum alanine transaminase total bilirubin concentrations predict CYP3A activity as measured by midazolam and 1'-hydroxylation.Medical science monitor : international medical journal of experimental and clinical research · 2015Article
- Xyloketal B, a marine compound, acts on a network of molecular proteins and regulates the activity and expression of rat cytochrome P450 3a: a bioinformatic and animal study.Drug design, development and therapy · 2014Article
- The effects of fall-risk-increasing drugs on postural control: a literature review.Drugs & aging · 2013Review
- Evaluation of limited sampling models for prediction of oral midazolam AUC for CYP3A phenotyping and drug interaction studies.European journal of clinical pharmacology · 2013Article
- Prediction of CYP3A4 enzyme activity using haplotype tag SNPs in African Americans.The pharmacogenomics journal · 2009Article
- Limitations of using a single postdose midazolam concentration to predict CYP3A-mediated drug interactions.Journal of clinical pharmacology · 2008Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundMidazolam (MDZ) is used as an assessment of human cytochrome P450 3A (CYP3A) activity. A single blood measurement is used as a marker of its activity based on an observed correlation between MDZ clearance and the 1'-hydroxymidazolam (1'-OH-MDZ): MDZ plasma ratio is assessed at 0.5 h followig the intake of a single 7.5 mg oral dose of MDZ in healthy young volunteers. In addition, a 4-h plasma MDZ measurement has been found to be an excellent predictor of AUC and CYP3A activity.
objectivesThe main aim of this study was to define a single-point blood sampling in healthy elderly volunteers. The secondary objective was to investigate the pharmacological effects of a low oral dose of MDZ (5 mg) and its potential psychometric changes.
methodsEight healthy elderly Caucasian volunteers participated in a single-dose, open-label, non-comparative study. Each subject received a single 5 mg oral dose of MDZ. Plasma concentrations of MDZ and its major metabolite, 1'-OH-MDZ, were assayed over 12 h. Secondary assessments of critical flicker fusion (CFF), body sway and mini-mental state examination were also carried out during the 12-h post-administration period.
resultsA moderate correlation was observed between MDZ clearance and the 1'-OH-MDZ: MDZ plasma concentration ratio at 9 h post-dosing (Rho=0.81; p=0.04), but an even better correlation (Rho=0.99; p<0.009) was found between MDZ AUC and MDZ plasma concentration at 6 h post-dosing, with the latter value corresponding approximately to the average mean residence time (MRT) determined in our trial. This study was well-tolerated despite a significant transitory decrease (relative to baseline) in cortical arousal at 1 h post-dosing, as assessed by CFF, and a non-significant decrease (relative to baseline) in balance and vigilance also measured at 1 h and assessed on body sway, compared to baseline values.
conclusionDespite the small sample size, based on the results of healthy, elderly volunteers, a single MDZ plasma measurement taken at 6 h post-oral administration may represent an accurate marker of CYP3A phenotype. This single-time-point method could be used safely for predicting drug-drug or diet interactions and identifying individuals with genetic polymorphism that affect CYP3A activity.
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