ArticleEuropean journal of drug metabolism and pharmacokinetics2023
Effect of Verapamil, a P-glycoprotein-1 and Cytochrome P450 3A4 Inhibitor, on Pharmacokinetics and Metabolic Stability of Ripretinib: A Drug-Drug Interaction Study in Rats.
Article in European journal of drug metabolism and pharmacokinetics, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 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
2 citing papers in PubMed, 5 citations in OpenAlex.
- Development and Validation of a LC-MS/MS Method for Ripretinib and Its Metabolite: Example of a Journey From Laboratory Bench to Routine Application With a Greenness Assessment.Biomedical chromatography : BMC · 2025Article
- Liquid chromatography-tandem mass spectrometry for the quantification of ripretinib and its metabolites DP-5439 in human plasma.Frontiers in pharmacology · 2024Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
2 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
BACKGROUND AND
objectivesRipretinib was developed to target a whole range of KIT proto-oncogene mutations and platelet-derived growth factor receptor A (PDGFR-A) kinases found in certain cancers and myeloproliferative neoplasms, particularly gastrointestinal stromal tumours (GISTs). This study investigated the effect of verapamil, a potential inhibitor of P-glycoprotein-1 (P-gp1) and cytochrome P450 3A4 (CYP3A4), on the pharmacokinetics of ripretinib in rats when administered orally together. This study also assessed the metabolic stability and in vitro cellular absorption of ripretinib in the presence of verapamil.
methodsA novel sensitive time-saving liquid chromatography tandem mass spectometry (LC-MS/MS) technique for determining ripretinib in rat plasma was developed and validated. A Zorbax SB C18 column was used for the separation and analysis of ripretinib with a mobile phase consisting of 50:50 (%v/v) acetonitrile and 10 mM ammonium formate buffer at a flow rate of 0.4 mL/min. Imatinib was used as an internal standard (IS) in the method. The pharmacokinetic characteristics of ripretinib were evaluated in Wistar rats by successfully administering an oral dosage of 5 mg/kg body weight of ripretinib in the presence of verapamil (10 mg/kg body weight). Subsequently, rat liver microsomes were used to assess the effect of verapamil on ripretinib metabolic stability, and absorption was tested using a Caco-2 cell transwell model.
resultsRipretinib and IS were identified using multiple reaction monitoring (MRM) modes by mass spectrometry and showed ion transitions of 510.09→94.06 m/z and 494.26→ 394.16 m/z, respectively. The high-performance liquid chromatography (HPLC) method successfully eluted ripretinib and IS at retention times of 0.91 and 0.68 min, respectively, and the method was validated for all parameters and met the criteria for acceptance. Co-administration of verapamil increased the maximum concentration (C
conclusionThe study results indicate that the co-administration of ripretinib with CYP3A4 and/or P-gp1 inhibitors is associated with significant drug-drug interactions that affect the pharmacokinetics of ripretinib. Further research in human subjects is suggested to confirm dosage adjustment and therapeutic drug monitoring of ripretinib when administered along with P-gp1/CYP3A4 inhibitors ensuring patient safety and optimizing the therapeutic benefits of ripretinib.
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.