AI Article Synopsis
- - Regorafenib helps improve survival in patients with metastatic colorectal cancer but can cause serious side effects that might necessitate changes in dosage or treatment schedules.
- - The drug is processed in the liver, leading to active metabolites M-2 and M-5, which have a much lower protein binding compared to regorafenib itself.
- - Higher plasma concentrations of M-2 and M-5 correlated with shorter progression-free survival, suggesting that side effects, particularly during the first treatment cycle, can lead to discontinuation of the drug.
Article Abstract
Regorafenib treatment improves survival of patients with metastatic colorectal cancer, but it is also characterized by detrimental side effects that may require modified dosing or interval schedules. Regorafenib is metabolized by cytochrome P450 3A4 in the liver to its active metabolites, M-2 and M-5. We examined area under the unbound plasma concentration-time curve (AUCu) to these compounds to establish pharmacokinetic bases for individualized dosing strategies. The plasma protein binding of M-2 and M-5 was approximately 10-fold lower than that of regorafenib, whereas AUCu values for active metabolites on both days 1 and 15 were significantly higher than that of regorafenib. Patients with higher AUCu values of M-2 or M-5 on day 1 showed significantly shorter progression-free survival than others, likely due, at least in part, to treatment discontinuation as a result of adverse events, especially occurred during first cycle.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1002/cpt.1810 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Pharmacognistic, proximate and phytochemical analysis of stem of Cistanche tubulosa (Schenck) Hook. F.
Cell Mol Biol (Noisy-le-grand)
January 2025
Department of Chemistry, Rabigh College of Sciences and Arts, King Abdulaziz University, Jeddah 21589, Saudi Arabia.
A medicinal plant is any plant that in one or more of its organs contains substances that can be used by it or their constituent for therapeutic purposes. The present work was done to evaluate pharmacognostic, fluorescence, proximate and phytochemical analysis of ethanolic extracts of Cistanche tubulosa (Orobanchaceae) along with antimicrobial activity. Antimicrobial activity against four bacterial strains S.
View Article and Find Full Text PDFMetabolomic Analysis of Patients With Patent Foramen Ovale and Migraine Using Liquid Chromatography-Mass Spectrometry Technology.
Rapid Commun Mass Spectrom
March 2025
Department of Cardiology, Xinjiang Traditional Chinese Medicine Hospital, Xinjiang, China.
Objective: This study aims to examine the changes in metabolic profiles in patients with patent foramen ovale (PFO) and migraine, as well as in patients with isolated migraine, before and after surgical intervention using metabolomics.
Methods: Patients were categorized into four groups: the simple migraine (SM) group, the PFO with migraine preoperative group (PRE), the PFO with migraine postoperative Day 3 group (POST_3d), and the PFO with migraine postoperative Day 30 group (POST_30d). Untargeted metabolomics using liquid chromatography-mass spectrometry (LC-MS) were employed to identify differential metabolites across these groups.
Cadmium translocation combined with metabolomics analysis revealed potential mechanisms of MT@MSN-CS and GSH@MSN-CS in reducing cadmium accumulation in rice (Oryza sativa L.) grains.
Environ Sci Pollut Res Int
January 2025
Key Laboratory of Water Pollution Control and Environmental Safety of Zhejiang Province, Department of Environmental Engineering, Zhejiang University, Zhejiang Province, Hangzhou, 310058, P.R. China.
Applying nano-delivery systems for phytohormones via foliar application has proven effective in reducing grain cadmium (Cd) levels in crops. However, the mechanisms underlying this reduction remain inadequately understood. This study integrated the determination of leaf photosynthetic parameters, Cd translocation analysis, and metabolomics to elucidate the effects of reduced glutathione (GSH) and melatonin (MT), delivered with or without chitosan-encapsulated mesoporous silica nanoparticles (MSN-CS), on grain Cd levels in rice.
View Article and Find Full Text PDFPost-COVID metabolic enzyme alterations in K18-hACE2 mice exacerbate alcohol-induced liver injury through transcriptional regulation.
Free Radic Biol Med
January 2025
Korea Mouse Phenotyping Center, Seoul National University, Seoul 08826, Republic of Korea; Laboratory of Developmental Biology and Genomics, Research Institute for Veterinary Science, and BK21 PLUS Program for Creative Veterinary Science Research, College of Veterinary Medicine, Seoul National University, Seoul 08826, Republic of Korea; Interdisciplinary Program for Bioinformatics, Program for Cancer Biology and BIO-MAX/N-Bio Institute, Seoul National University, Seoul 08826, Republic of Korea. Electronic address:
Coronavirus disease (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), poses a significant threat to global public health. Despite reports of liver injury during viral disease, the occurrence and detailed mechanisms underlying the development of secondary exogenous liver injury, particularly in relation to changes in metabolic enzymes, remain to be fully elucidated. Therefore, this study was aimed to investigate the mechanisms underlying SARS-CoV-2-induced molecular alterations in hepatic metabolism and the consequent secondary liver injury resulting from alcohol exposure.
View Article and Find Full Text PDFEffects of colloids with different compositions on benzophenone-3 biotoxicity in zebrafish embryos.
Environ Pollut
January 2025
Water Resources Research Institute of Shandong Province, Shandong Province Key Lab Water Resources & Environment, Jinan 250000, China.
The fate of the pollutants in aquatic environment is closely related to colloids, and the carrier effect of colloids on pollutants not only affects their bioaccumulation, but may also affect their toxicity. In this study, the effects of natural colloid with different components on the biological toxicity of benzophenone-3 (BP3) to zebrafish larvae (Diano rerio) were studied. BP3 caused oxidative stress damage, thyroid system disorders and neurotoxicity in zebrafish larvae.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!