ArticleEuropean journal of clinical pharmacology2004
Identification of cytochrome P450 isoforms involved in the metabolism of loperamide in human liver microsomes.
Article 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. It is linked to trial NCT04186936 (An Open-label, Randomized, Fasting, Two-period, Single-dose, Crossover Study to Assess Bioequivalence Between a Combination Caplet With Loperamide Hydrochloride and Simethicone), which is not on this map. Cited by 21 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.
An Open-label, Randomized, Fasting, Two-period, Single-dose, Crossover Study to Assess Bioequivalence Between a Combination Caplet With Loperamide Hydrochloride and Simethicone (Janssen-Cilag, France), and Imodium® Express Tablets-lyophilizate (Janssen-Cilag, France) Coadministered With Espumisan® Capsule (Berlin-Chemie AG, Germany), in Healthy Volunteers
Who cites it
21 citing papers in PubMed, 82 citations in OpenAlex.
- Assessment of a candidate marker constituent predictive of a dietary substance-drug interaction: case study with grapefruit juice and CYP3A4 drug substrates.The Journal of pharmacology and experimental therapeutics · 2014Trial
- Prospective randomized double-blind trial of racecadotril compared with loperamide in elderly people with gastroenteritis living in nursing homes.European journal of clinical pharmacology · 2010Trial
- Short-term effect of quercetin on the pharmacokinetics of fexofenadine, a substrate of P-glycoprotein, in healthy volunteers.European journal of clinical pharmacology · 2009Trial
- Itraconazole, gemfibrozil and their combination markedly raise the plasma concentrations of loperamide.European journal of clinical pharmacology · 2006Trial
- Managing Drug-Drug Interactions Involving the Non-Prescription Opioid Loperamide Through Physiologically Based Pharmacokinetic Modeling.CPT: pharmacometrics & systems pharmacology · 2026Article
- Designing a Small Molecule for PET Radiotracing: [Molecules (Basel, Switzerland) · 2025Review
- Perspectives of and Experience toward the Abuse of Antidiarrheal Drug (Loperamide) among Community Pharmacists: A Cross-Sectional Study.International journal of environmental research and public health · 2023Article
- No relation between docetaxel administration route and high-grade diarrhea incidence.Pharmacology research & perspectives · 2020Article
- Functional characteristics of CYP3A4 allelic variants on the metabolism of loperamide in vitro.Infection and drug resistance · 2019Article
- Pharmacologic Treatment of Opioid Use Disorder: a Review of Pharmacotherapy, Adjuncts, and Toxicity.Journal of medical toxicology : official journal of the American College of Medical Toxicology · 2018Review
- Ventricular Tachycardia Triggered by Loperamide and Famotidine Abuse.Drug safety - case reports · 2018Article
- MSBIS: A Multi-Step Biomedical Informatics Screening Approach for Identifying Medications that Mitigate the Risks of Metoclopramide-Induced Tardive Dyskinesia.EBioMedicine · 2017Article
- High-dose loperamide abuse-associated ventricular arrhythmias.HeartRhythm case reports · 2016Article
- "Target-Site" Drug Metabolism and Transport.Drug metabolism and disposition: the biological fate of chemicals · 2015Article
- Article
- Sucralose, a synthetic organochlorine sweetener: overview of biological issues.Journal of toxicology and environmental health. Part B, Critical reviews · 2013Review
- CYP isoform specificity toward drug metabolism: analysis using common feature hypothesis.Journal of molecular modeling · 2012Article
- Effects of ketoconazole on the biodistribution and metabolism of [11C]loperamide and [11C]N-desmethyl-loperamide in wild-type and P-gp knockout mice.Nuclear medicine and biology · 2010Article
- Cytochrome P450 2C8 pharmacogenetics: a review of clinical studies.Pharmacogenomics · 2009Article
- Role of active metabolites in the use of opioids.European journal of clinical pharmacology · 2009Review
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
objectiveThe purpose of the present study was to elucidate the cytochrome P450 (P450) isoform(s) involved in the metabolism of loperamide (LOP) to N-demethylated LOP (DLOP) in human liver microsomes.
methodsThree established approaches were used to identify the P450 isoforms responsible for LOP N-demethylation using human liver microsomes and cDNA-expressed P450 isoforms: (1) correlation of LOP N-demethylation activity with marker P450 activities in a panel of human liver microsomes, (2) inhibition of enzyme activity by P450-selective inhibitors, and (3) measurement of DLOP formation by cDNA-expressed P450 isoforms. The relative contribution of P450 isoforms involved in LOP N-demethylation in human liver microsomes were estimated by applying relative activity factor (RAF) values.
resultsThe formation rate of DLOP showed biphasic kinetics, suggesting the involvement of multiple P450 isoforms. Apparent Km and Vmax values were 21.1 microM and 122.3 pmol/min per milligram of protein for the high-affinity component and 83.9 microM and 412.0 pmol/min per milligram of protein for the low-affinity component, respectively. Of the cDNA-expressed P450 s tested, CYP2B6, CYP2C8, CYP2D6, and CYP3A4 catalyzed LOP N-demethylation. LOP N-demethylation was significantly inhibited when coincubated with quercetin (a CYP2C8 inhibitor) and ketoconazole (a CYP3A4 inhibitor) by 40 and 90%, respectively, but other chemical inhibitors tested showed weak or no significant inhibition. DLOP formation was highly correlated with CYP3A4-catalyzed midazolam 1-hydroxylation (rs=0.829; P<0.01), CYP2B6-catalzyed 7-ethoxy-4-trifluoromethylcoumarin O-deethylation (rs=0.691; P<0.05), and CYP2C8-catalyzed paclitaxel 6alpha-hydroxylation (rs=0.797; P<0.05).
conclusionCYP2B6, CYP2C8, CYP2D6, and CYP3A4 catalyze LOP N-demethylation in human liver microsomes, and among them, CYP2C8 and CYP3A4 may play a crucial role in LOP metabolism at the therapeutic concentrations of LOP. Coadministration of these P450 inhibitors may cause drug interactions with LOP. However, the clinical significance of potential interaction of LOP metabolism by CYP2C8 and CYP3A4 inhibitors should be studied further.
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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 OpenQuestion graph.