ArticleClinical pharmacokinetics2022
Evaluation of Absorption and Metabolism-Based DDI Potential of Pexidartinib in Healthy Subjects.
Article in Clinical pharmacokinetics, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT03138759 (An Open-label, Randomized, 2-treatment, 2-period, Crossover Study to Evaluate the Effect of Probenecid on the Pharmacokinetics of Pexidartinib in Healthy Subjects), which is not on this map. Cited by 8 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.
An Open-label, Randomized, 2-treatment, 2-period, Crossover Study to Evaluate the Effect of Probenecid on the Pharmacokinetics of Pexidartinib in Healthy Subjects
Who cites it
8 citing papers in PubMed, 11 citations in OpenAlex.
- The Effect of Ecopipam on the Pharmacokinetics of Concomitant Medications.Clinical and translational science · 2026Article
- Characterizing the metabolites of the tyrosine-kinase inhibitor pexidartinib in mouse feces, urine, plasma, and liver.Journal of pharmaceutical and biomedical analysis · 2025Article
- Mechanistic study of pexidartinib-induced toxicity in human hepatic cells.Chemico-biological interactions · 2025Article
- A disproportionality analysis of adverse events caused by pexidartinib from the FDA adverse event reporting system.Scientific reports · 2025Article
- Review
- The Effect of Drug-Drug Interactions on the Pharmacokinetics of Isavuconazole: A Comprehensive Review.Clinical pharmacology : advances and applications · 2025Review
- An open-label study to explore the optimal design of CYP3A drug-drug interaction clinical trials in healthy Chinese people.Pharmacology research & perspectives · 2024Article
- Identifying the Reactive Metabolites of Tyrosine Kinase Inhibitor Pexidartinib In Vitro Using LC-MS-Based Metabolomic Approaches.Chemical research in toxicology · 2023Article
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
BACKGROUND AND
objectivePexidartinib is a novel oral small-molecule inhibitor that selectively targets colony-stimulating factor 1 receptor, KIT proto-oncogene receptor tyrosine kinase, and FMS-like tyrosine kinase 3 harboring an internal tandem duplication mutation. It is approved in the United States for the treatment of adult patients with symptomatic tenosynovial giant cell tumor (TGCT) associated with severe morbidity or functional limitations and not amenable to improvement with surgery. Pexidartinib in vitro data indicate the potential for absorption- and metabolism-related drug-drug interactions (DDIs). The objective was to present a comprehensive DDI risk assessment of agents that can impact pexidartinib exposure by altering its absorption and metabolism potentially affecting efficacy and safety of pexidartinib.
methodsFour open-label crossover studies were performed to assess the effects of a pH modifier (esomeprazole), a strong cytochrome P450 (CYP) 3A4 inhibitor (itraconazole), a strong CYP3A/5'-diphospho-glucuronosyltransferase (UGT) inducer (rifampin), and a UGT inhibitor (probenecid) on the single-dose pharmacokinetics of pexidartinib. In addition, a physiologically based pharmacokinetic model was developed to predict the effect of a moderate CYP3A4 inhibitor (fluconazole) and a moderate CYP3A inducer (efavirenz) on the pharmacokinetics of pexidartinib.
resultsCo-administration of pexidartinib with esomeprazole modestly decreased pexidartinib exposure (maximum plasma concentration [C
conclusionsThe physiologically based pharmacokinetic model predicted that a moderate CYP3A4 inhibitor and a moderate CYP3A inducer would produce modest increases and decreases, respectively, in pexidartinib exposure. These results provide a basis for pexidartinib dosing recommendations when administered concomitantly with drugs with drug-drug interaction potential, including dose adjustments when concomitant administration cannot be avoided. CLINICAL
trial registrationProbenecid: phase I trial, NCT03138759, 3 May, 2017; esomeprazole, itraconazole, rifampin: phase I trials, not registered with ClinicalTrials.gov.
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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.