ArticleCancer chemotherapy and pharmacology2021
Impact of fedratinib on the pharmacokinetics of transporter probe substrates using a cocktail approach.
Article in Cancer chemotherapy and pharmacology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT04231435 (A Phase 1, Open-label Study to Evaluate the Influence of Fedratinib on the Pharmacokinetics of Transporter Probe Substrates), which is not on this map. Cited by 9 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.
A Phase 1, Open-label Study to Evaluate the Influence of Fedratinib on the Pharmacokinetics of Transporter Probe Substrates (Digoxin, Rosuvastatin, and Metformin) in Healthy Adult Subjects
Who cites it
9 citing papers in PubMed, 18 citations in OpenAlex.
- Relative bioavailability of fedratinib through various alternative oral administration methods in healthy adults.Cancer chemotherapy and pharmacology · 2024Trial
- Review
- Fedratinib in chronic kidney disease: antifibrotic potential and renal safety signals from integrated network toxicology and pharmacovigilance.Renal failure · 2025Article
- Predicting OCT2/MATEs-Mediated Drug Interactions in Healthy Volunteers and Patients with Chronic Kidney Disease: Insights from Extended Clearance Concept, Endogenous Biomarkers, and In Vitro Inhibition Studies (Perspectives from the International Transporter Consortium).Clinical pharmacology and therapeutics · 2025Review
- Innovative Approaches to Optimize Clinical Transporter Drug-Drug Interaction Studies.Pharmaceutics · 2024Review
- Use of a Double-Transfected System to Predict hOCT2/hMATE1-Mediated Renal Drug-Drug Interactions.Drug metabolism and disposition: the biological fate of chemicals · 2024Article
- Effect of fluconazole on the pharmacokinetics of a single dose of fedratinib in healthy adults.Cancer chemotherapy and pharmacology · 2022Article
- Pharmacoproteomics of Brain Barrier Transporters and Substrate Design for the Brain Targeted Drug Delivery.Pharmaceutical research · 2022Review
- Impact of fedratinib on the pharmacokinetics of transporter probe substrates using a cocktail approach.Cancer chemotherapy and pharmacology · 2021Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
12 authors at 3 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
introductionFedratinib, an oral, selective Janus kinase 2 inhibitor, has been shown to inhibit P-glycoprotein (P-gp), breast cancer resistance protein (BCRP), organic anion transporting polypeptide (OATP) 1B1, OATP1B3, organic cation transporter (OCT) 2, and multidrug and toxin extrusion (MATE) 1 and MATE2-K in vitro. The objective of this study was to evaluate the influence of fedratinib on the pharmacokinetics (PK) of digoxin (P-gp substrate), rosuvastatin (OATP1B1/1B3 and BCRP substrate), and metformin (OCT2 and MATE1/2-K substrate).
methodsIn this nonrandomized, fixed-sequence, open-label study, 24 healthy adult participants received single oral doses of digoxin 0.25 mg, rosuvastatin 10 mg, and metformin 1000 mg administered as a drug cocktail (day 1, period 1). After a 6-day washout, participants received oral fedratinib 600 mg 1 h before the cocktail on day 7 (period 2). An oral glucose tolerance test (OGTT) was performed to determine possible influences of fedratinib on the antihyperglycemic effect of metformin.
resultsPlasma exposure to the three probe drugs was generally comparable in the presence or absence of fedratinib. Reduced metformin renal clearance by 36% and slightly higher plasma glucose levels after OGTT were observed in the presence of fedratinib. Single oral doses of the cocktail ± fedratinib were generally well tolerated.
conclusionsThese results suggest that fedratinib has minimal impact on the exposure of P-gp, BCRP, OATP1B1/1B3, OCT2, and MATE1/2-K substrates. Since renal clearance of metformin was decreased in the presence of fedratinib, caution should be exercised in using coadministered drugs that are renally excreted via OCT2 and MATEs.
trial registrationClinicaltrials.gov NCT04231435 on January 18, 2020.
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.