ArticleClinical and translational science2019
Interaction Between Sex and Organic Anion-Transporting Polypeptide 1b2 on the Pharmacokinetics of Regorafenib and Its Metabolites Regorafenib-N-Oxide and Regorafenib-Glucuronide in Mice.
Article in Clinical and translational science, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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
11 citing papers in PubMed, 15 citations in OpenAlex.
- Regulation of hepatic organic anion transporting polypeptide 1B-type transport function by the protein kinase LYN.Drug metabolism and disposition: the biological fate of chemicals · 2025Article
- OATP1B-type Transport Function Is a Determinant of Aromatase Inhibitor-Associated Arthralgia Susceptibility.Cancer research communications · 2025Article
- Pharmacokinetic Interaction Between Olaparib and Regorafenib in an Animal Model.Pharmaceutics · 2024Article
- 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
- A Metabolomics Approach for Predicting OATP1B-Type Transporter-Mediated Drug-Drug Interaction Liabilities.Pharmaceutics · 2022Article
- A Physiologically Based Pharmacokinetic and Drug-Drug Interaction Model for the CB2 Agonist Lenabasum.European journal of drug metabolism and pharmacokinetics · 2021Article
- The Role of Uptake and Efflux Transporters in the Disposition of Glucuronide and Sulfate Conjugates.Frontiers in pharmacology · 2021Review
- Population pharmacokinetics of regorafenib in solid tumours: Exposure in clinical practice considering enterohepatic circulation and food intake.British journal of clinical pharmacology · 2020Article
- Optimized low-dose combinatorial drug treatment boosts selectivity and efficacy of colorectal carcinoma treatment.Molecular oncology · 2020Article
- Targeting Regorafenib-Induced Toxicity through Inhibition of Gut Microbial β-Glucuronidases.ACS chemical biology · 2019Article
- Article
Corrections and comments
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
Regorafenib, a multikinase inhibitor used in the treatment of various solid tumors, undergoes extensive uridine 5'-diphosphate glucuronosyltransferase (Ugt)1a9-mediated glucuronidation to form regorafenib-N-β-glucuronide (M7; RG), but the contribution of hepatic uptake transporters, such as organic anion-transporting polypeptide (Oatp)1b2, to the pharmacokinetics of regorafenib remains poorly understood. Using NONMEM-based, population-based, parent-metabolite modeling, we found that Oatp1b2 and sex strongly impact the systemic exposure to RG in mice receiving oral regorafenib. Metabolic studies revealed that the liver microsomal expression of cytochrome P450 (Cyp)3a11 is twofold lower in female mice, whereas Ugt1a9 levels and function are not sex dependent. This finding is consistent with the metabolism of regorafenib occurring via two competing pathways, and the lack of Oatp1b2 results in decreased clearance of RG. The described model provides mechanistic insights into the in vivo disposition of regorafenib.
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Registered trials
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