ArticleBritish journal of clinical pharmacology2000
In vitro inhibition of the cytochrome P450 (CYP450) system by the antiplatelet drug ticlopidine: potent effect on CYP2C19 and CYP2D6.
Article in British journal of clinical pharmacology, 2000. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 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
31 citing papers in PubMed, 102 citations in OpenAlex.
- Ticlopidine inhibits both O-demethylation and renal clearance of tramadol, increasing the exposure to it, but itraconazole has no marked effect on the ticlopidine-tramadol interaction.European journal of clinical pharmacology · 2013Trial
- Cytochrome P450-mediated metabolism of K31, a Ko143-derived ATP-binding cassette subfamily G member 2 inhibitor.Drug metabolism and disposition: the biological fate of chemicals · 2026Article
- Exploring the roles of cytochrome P450 enzymes and their inhibitors in cancers and non-neoplastic human diseases.Archives of pharmacal research · 2025Review
- A Review on New Frontiers in Drug-Drug Interaction Predictions and Safety Evaluations with In Vitro Cellular Models.Pharmaceutics · 2025Review
- Development and Characterization of pFluor50, a Fluorogenic-Based Kinetic Assay System for High-Throughput Inhibition Screening and Characterization of Time-Dependent Inhibition and Inhibition Type for Six Human CYPs.Molecules (Basel, Switzerland) · 2025Article
- A Review of CYP-Mediated Drug Interactions: Mechanisms and In Vitro Drug-Drug Interaction Assessment.Biomolecules · 2024Review
- Development and Validation of a Novel HPLC Method to Analyse Metabolic Reaction Products Catalysed by the CYP3A2 Isoform: In Vitro Inhibition of CYP3A2 Enzyme Activity by Aspirin (Drugs Often Used Together in COVID-19 Treatment).Molecules (Basel, Switzerland) · 2022Article
- PBPK Analysis to Study the Impact of Genetic Polymorphism of NAT2 on Drug-Drug Interaction Potential of Isoniazid.Pharmaceutical research · 2021Article
- CYP3A4 Mediates Oxidative Metabolism of the Synthetic Cannabinoid AKB-48.The AAPS journal · 2015Article
- Linear Interaction Energy Based Prediction of Cytochrome P450 1A2 Binding Affinities with Reliability Estimation.PloS one · 2015Article
- Enantioselectivity in the cytochrome P450-dependent conversion of tegafur to 5-fluorouracil in human liver microsomes.Pharmacology research & perspectives · 2013Article
- In vitro metabolism of piperaquine is primarily mediated by CYP3A4.Xenobiotica; the fate of foreign compounds in biological systems · 2012Article
- Cytochrome P450 2C24: Expression, Tissue Distribution, High-Throughput Assay, and Pharmacological Inhibition.Acta pharmaceutica Sinica. B · 2012Article
- Optimizing of thienopyridine therapy by multiple electrode platelet aggregometry in clopidogrel low responders undergoing PCI.Clinical research in cardiology : official journal of the German Cardiac Society · 2011Article
- Effects of ticlopidine on pharmacokinetics of losartan and its main metabolite EXP-3174 in rats.Acta pharmacologica Sinica · 2011Article
- Chemical inhibitors of cytochrome P450 isoforms in human liver microsomes: a re-evaluation of P450 isoform selectivity.European journal of drug metabolism and pharmacokinetics · 2011Review
- Comparison of in vitro metabolism of ticlopidine by human cytochrome P450 2B6 and rabbit cytochrome P450 2B4.Drug metabolism and disposition: the biological fate of chemicals · 2011Article
- Stereo-selective metabolism of methadone by human liver microsomes and cDNA-expressed cytochrome P450s: a reconciliation.Basic & clinical pharmacology & toxicology · 2011Article
- Coprescription of tamoxifen and medications that inhibit CYP2D6.Journal of clinical oncology : official journal of the American Society of Clinical Oncology · 2010Review
- Comprehensive in vitro analysis of voriconazole inhibition of eight cytochrome P450 (CYP) enzymes: major effect on CYPs 2B6, 2C9, 2C19, and 3A.Antimicrobial agents and chemotherapy · 2009Article
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 2 institutions in 1 country.
Funding
Abstract
aimsTo examine the potency of ticlopidine (TCL) as an inhibitor of cytochrome P450s (CYP450s) in vitro using human liver microsomes (HLMs) and recombinant human CYP450s.
methodsIsoform-specific substrate probes of CYP1A2, 2C19, 2C9, 2D6, 2E1 and 3A4 were incubated in HLMs or recombinant CYPs with or without TCL. Preliminary data were generated to simulate an appropriate range of substrate and inhibitor concentrations to construct Dixon plots. In order to estimate accurately inhibition constants (Ki values) of TCL and determine the type of inhibition, data from experiments with three different HLMs for each isoform were fitted to relevant nonlinear regression enzyme inhibition models by WinNonlin.
resultsTCL was a potent, competitive inhibitor of CYP2C19 (Ki = 1.2 +/- 0.5 microM) and of CYP2D6 (Ki = 3.4 +/- 0.3 microM). These Ki values fell within the therapeutic steady-state plasma concentrations of TCL (1-3 microM). TCL was also a moderate inhibitor of CYP1A2 (Ki = 49 +/- 19 microM) and a weak inhibitor of CYP2C9 (Ki > 75 microM), but its effect on the activities of CYP2E1 (Ki = 584 +/- 48 microM) and CYP3A (> 1000 microM) was marginal.
conclusionsTCL appears to be a broad-spectrum inhibitor of the CYP isoforms, but clinically significant adverse drug interactions are most likely with drugs that are substrates of CYP2C19 or CYP2D6.
Indexed as
Identifiers
What OpenQuestion 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 OpenQuestion graph.