ArticlePharmaceutical research2003
Midazolam exhibits characteristics of a highly permeable P-glycoprotein substrate.
Article in Pharmaceutical research, 2003. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 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
27 citing papers in PubMed, 80 citations in OpenAlex.
- Indinavir Increases MidazolamDrug metabolism and disposition: the biological fate of chemicals · 2019Trial
- Evaluation of CYP3A activity in humans using three different parameters based on endogenous cortisol metabolism.Acta pharmacologica Sinica · 2009Trial
- Variations of CYP3A activity induced by antiretroviral treatment in HIV-1 infected patients.European journal of clinical pharmacology · 2005Trial
- Oral administration of a low dose of midazolam (75 microg) as an in vivo probe for CYP3A activity.European journal of clinical pharmacology · 2004Trial
- Proteomic and functional profiling of suspended jejunal enteroids reveals pharmacokinetic fidelity to native intestine.iScience · 2026Article
- Downregulation of hepatic CYP3A isoforms by bardoxolone methyl in rats and its impact on in vivo metabolic capacity reflecting pharmacokinetics.Scientific reports · 2026Article
- Analysis of the Correlation Between Membrane Permeability in RPMI 2650 Cells and Human Nasal Absorption.AAPS PharmSciTech · 2026Article
- A primary human Gut/Liver microphysiological system to estimate human oral bioavailability.Drug metabolism and disposition: the biological fate of chemicals · 2025Article
- Translating Molecular Psychiatry: From Biomarkers to Personalized Therapies-A Narrative Review.International journal of molecular sciences · 2025Review
- Pharmacokinetics, Pharmacodynamics, and Side Effects of Midazolam: A Review and Case Example.Pharmaceuticals (Basel, Switzerland) · 2024Review
- Pharmacogenomics of Dementia: Personalizing the Treatment of Cognitive and Neuropsychiatric Symptoms.Genes · 2023Review
- The Role of Pharmacogenetics in Personalizing the Antidepressant and Anxiolytic Therapy.Genes · 2023Review
- A Critical Overview of the Biological Effects of Excipients (Part I): Impact on Gastrointestinal Absorption.The AAPS journal · 2022Review
- Estimation of Fetal-to-Maternal Unbound Steady-State Plasma Concentration Ratio of P-Glycoprotein and/or Breast Cancer Resistance Protein Substrate Drugs Using a Maternal-Fetal Physiologically Based Pharmacokinetic Model.Drug metabolism and disposition: the biological fate of chemicals · 2022Article
- Influence of midazolam-related genetic polymorphism on conscious sedation during upper gastrointestinal endoscopy in a Korean population.Scientific reports · 2019Observational
- Development of a Novel Maternal-Fetal Physiologically Based Pharmacokinetic Model II: Verification of the model for passive placental permeability drugs.Drug metabolism and disposition: the biological fate of chemicals · 2017Article
- Review
- A physiologically based pharmacokinetic model to predict the pharmacokinetics of highly protein-bound drugs and the impact of errors in plasma protein binding.Biopharmaceutics & drug disposition · 2016Article
- To Apply Microdosing or Not? Recommendations to Single Out Compounds with Non-Linear Pharmacokinetics.Clinical pharmacokinetics · 2016Article
- Pharmacokinetics of paracetamol in Göttingen minipigs: in vivo studies and modeling to elucidate physiological determinants of absorption.Pharmaceutical research · 2014Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 3 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
purposeThe purpose of this study was to investigate whether midazolam exhibits characteristics of a highly permeable P-glycoprotein (P-gp) substrate and to evaluate the potential influence of P-gp inhibition on 1-OH midazolam formation during midazolam transport.
methodsP-gp interaction was investigated by P-gp ATPase assay, efflux inhibition studies, and transport studies of midazolam across MDR1-MDCK and 1-alpha,25-dihydroxy vitamin D3-induced Caco-2 monolayers with and without the P-gp inhibitor GF120918.
resultsMidazolam was highly permeable and transport appeared essentially unpolarized. In MDR1-MDCK, the basolateral-to-apical (B-to-A) permeability was slightly higher (16%) than apical-to-basolateral (A-to-B) permeability (p = 0.04); GF120918 increased A-to-B permeability by 27% (p = 0.01), and increased cellular midazolam accumulation during A-to-B transport by 45% (p = 0.01). Midazolam (200 microM) decreased rhodamine123 and vinblastine B/A ratios 3-fold (p < 0.006), while increasing their cellular accumulation (p < 0.003). P-gp ATPase activation by midazolam was dose-dependent and saturable [Km = 11.5(+/- 4.0) microM; Vmax = 41.1(+/- 7.4) nmol/mg/min]. P-gp inhibition increased 1-OH midazolam formation in A-to-B studies 1.3-fold when midazolam donor > or = 10 microM (p < 0.03). In B-to-A studies, P-gp inhibition did not significantly increase metabolite formation (p = 0.06). Midazolam's extraction ratio was not influenced by P-gp (p = 0.2).
conclusionThe results indicate that midazolam exhibited characteristics of a highly permeable P-gp substrate. 1-OH midazolam formation during A-to-B midazolam transport increased slightly when P-gp was inhibited.
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Registered trials
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