ArticleBritish journal of clinical pharmacology2020
Population pharmacokinetics of regorafenib in solid tumours: Exposure in clinical practice considering enterohepatic circulation and food intake.
Article in British journal of clinical pharmacology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers, 1 of them a synthesis that pooled it.
What it found
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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.
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Who cites it
16 citing papers in PubMed, 1 synthesis or guideline pooled it, 33 citations in OpenAlex.
- Pooled it
- Impact of trough concentrations of regorafenib and its major metabolites M-2 and M-5 on overall survival of chemorefractory metastatic colorectal cancer patients: Results from a multicentre GERCOR TEXCAN phase II study.European journal of cancer (Oxford, England : 1990) · 2022Trial
- Bioequivalence and Pharmacokinetic Evaluation of Two Oral Formulations of Regorafenib: An Open-Label, Randomised, Single-Dose, Two-Period, Two-Way Crossover Clinical Trial in Healthy Chinese Volunteers Under Fasting and Fed Conditions.Drug design, development and therapy · 2021Trial
- A multicenter dose-defining/expansion phase 1b study of first-line regorafenib plus pembrolizumab in patients with advanced hepatocellular carcinoma.Hepatology (Baltimore, Md.) · 2026Article
- Unraveling regorafenib resistance: metabolic reprogramming, tumor plasticity, and novel approaches to overcome therapy failure.Archives of pharmacal research · 2026Review
- Development of a UPLC-MS/MS method and its application for the pharmacokinetic analysis of regorafenib in rats.Scientific reports · 2026Article
- Sex differences in hepatic enzymes and transporters involved in pharmacokinetics.Liver research (Beijing, China) · 2025Review
- A Review of FDA-Approved Multi-Target Angiogenesis Drugs for Brain Tumor Therapy.International journal of molecular sciences · 2025Review
- Real-world safety profile and mechanistic insights into regorafenib-induced liver failure: a pharmacovigilance study integrated with network toxicology.Frontiers in pharmacology · 2025Article
- Association between albumin-bilirubin grade and plasma trough concentrations of regorafenib and its metabolites M-2 and M-5 at steady-state in Japanese patients.Investigational new drugs · 2024Article
- Regorafenib plus Vincristine and Irinotecan in Pediatric Patients with Recurrent/Refractory Solid Tumors: An Innovative Therapy for Children with Cancer Study.Clinical cancer research : an official journal of the American Association for Cancer Research · 2023Article
- Effects of regorafenib on the mononuclear/phagocyte system and how these contribute to the inhibition of colorectal tumors in mice.European journal of medical research · 2023Article
- Pharmacokinetics of the oral multikinase inhibitor regorafenib and its association with real-world treatment outcomes.Investigational new drugs · 2021Article
- How to Treat Hepatocellular Carcinoma in Elderly Patients.Pharmaceuticals (Basel, Switzerland) · 2021Review
- Feasibility of Extrapolating Randomly Taken Plasma Samples to Trough Levels for Therapeutic Drug Monitoring Purposes of Small Molecule Kinase Inhibitors.Pharmaceuticals (Basel, Switzerland) · 2021Article
- Population pharmacokinetics of regorafenib in solid tumours: Exposure in clinical practice considering enterohepatic circulation and food intake.British journal of clinical pharmacology · 2020Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
aimRegorafenib is an oral multikinase inhibitor with clinical efficacy in a range of advanced solid tumours. A population pharmacokinetic (PK) model was developed to evaluate the variability of the PK of regorafenib and its pharmacologically active metabolites M-2 and M-5 in solid tumours.
methodsThe model was initially developed using densely sampled phase 1 data and information on food intake to incorporate enterohepatic circulation (EHC) that was identified to considerably contribute to the PK of regorafenib. This was then applied to sparsely sampled data from four phase 3 studies in patients with advanced solid tumours. The need for exact food intake data to estimate individual drug exposure was evaluated.
resultsBy incorporating EHC, the model adequately described the PK profiles of regorafenib, M-2 and M-5 after single and multiple doses in patients from phase 1 studies. Individual exposure in phase 3 studies was adequately described based on assumptions on the time and frequency of food intake, although exact food intake data are recommended to improve the estimation. Covariate analysis identified sex and body mass index (BMI) as impacting exposure to regorafenib, and sex as strongly impacting exposure to M-2 and M-5 (also influenced by the BMI effect on parent regorafenib in the joint model developed); however, these factors accounted for a small portion of the overall variability in exposure.
conclusionsThe adequate description of regorafenib PK after multiple dosing requires the incorporation of EHC. Neither single nor combined covariates predicted exposures that would warrant a priori regorafenib dose adjustment.
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