ArticleBiomolecules2022
Midazolam as a Probe for Heterotropic Drug-Drug Interactions Mediated by CYP3A4.
Article in Biomolecules, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
10 citing papers in PubMed, 17 citations in OpenAlex.
- A Novel Technology Platform for Extracellular Vesicle-Targeted Expression of Drug-Metabolizing Enzymes: Driving CYP3A4 Expression and Secretion via the EABR Motif.Biomedicines · 2026Article
- Lipid Dependence of CYP3A4 Activity in Nanodiscs.Biology · 2026Article
- Quantifying expression and metabolic activity of genes regulated by pregnane X receptor in primary human hepatocyte spheroids.PLoS computational biology · 2025Article
- Precision medication based on the evaluation of drug metabolizing enzyme and transporter functions.Precision clinical medicine · 2025Review
- Pharmacokinetic drug-drug interactions of JBPOS0101 mediated by cytochrome P450 3A4 and UDP-glucuronosyltransferases.Clinical and translational science · 2024Article
- EIDD-1931 Treatment Tweaks CYP3A4 and CYP2C8 in Arthritic Rats to Expedite Drug Interaction: Implication in Oral Therapy of Molnupiravir.ACS omega · 2024Article
- Factors influencing the detergent-free membrane protein isolation using synthetic nanodisc-forming polymers.Biochimica et biophysica acta. Biomembranes · 2024Article
- Pharmacokinetics study of atracurium, dexmedetomidine, midazolam and 1-hydroxymidazolam in patients undergoing acute aortic dissection surgery.Frontiers in pharmacology · 2024Article
- Pharmacogenomics of Dementia: Personalizing the Treatment of Cognitive and Neuropsychiatric Symptoms.Genes · 2023Review
- Detergent-Free Isolation of Membrane Proteins and Strategies to Study Them in a Near-Native Membrane Environment.Biomolecules · 2022Review
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 1 institution in 1 country.
Funding
Abstract
Human cytochrome P450 CYP3A4 is involved in the processing of more than 35% of current pharmaceuticals and therefore is responsible for multiple drug-drug interactions (DDI). In order to develop a method for the detection and prediction of the possible involvement of new drug candidates in CYP3A4-mediated DDI, we evaluated the application of midazolam (MDZ) as a probe substrate. MDZ is hydroxylated by CYP3A4 in two positions: 1-hydroxy MDZ formed at lower substrate concentrations, and up to 35% of 4-hydroxy MDZ at high concentrations. The ratio of the formation rates of these two products (the site of metabolism ratio, SOM) was used as a measure of allosteric heterotropic interactions caused by effector molecules using CYP3A4 incorporated in lipid nanodiscs. The extent of the changes in the SOM in the presence of effectors is determined by chemical structure and is concentration-dependent. MD simulations of CYP3A4 in the lipid bilayer suggest that experimental results can be explained by the movement of the F-F' loop and concomitant changes in the shape and volume of the substrate-binding pocket. As a result of PGS binding at the allosteric site, several residues directly contacting MDZ move away from the substrate molecule, enabling the repositioning of the latter for minor product formation.
Indexed as
Identifiers
What Socratic holds
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 Socratic graph.