SynthesisEuropean journal of clinical pharmacology2012
Meta-analysis of contribution of genetic polymorphisms in drug-metabolizing enzymes or transporters to axitinib pharmacokinetics.
Synthesis in European journal of clinical pharmacology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
What it found
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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
22 citing papers in PubMed.
- Contribution of UGT1A1 genetic polymorphisms related to axitinib pharmacokinetics to safety and efficacy in patients with renal cell carcinoma.Medical oncology (Northwood, London, England) · 2018Trial
- Efficacy and safety of axitinib versus sorafenib in metastatic renal cell carcinoma: subgroup analysis of Japanese patients from the global randomized Phase 3 AXIS trial.Japanese journal of clinical oncology · 2013Trial
- Influence of genetic polymorphisms in vascular endothelial-related genes on the clinical outcome of axitinib in patients with metastatic renal cell carcinoma.Cancer biology & therapy · 2024Article
- A Profile of Avelumab Plus Axitinib in the Treatment of Renal Cell Carcinoma.Therapeutics and clinical risk management · 2022Review
- Absorption of the orally active multikinase inhibitor axitinib as a therapeutic index to guide dose titration in metastatic renal cell carcinoma.Investigational new drugs · 2021Article
- Influence of Genetic Variants on Steady-State Etonogestrel Concentrations Among Contraceptive Implant Users.Obstetrics and gynecology · 2019Article
- The FDA approved PI3K inhibitor GDC-0941 enhances in vitro the anti-neoplastic efficacy of Axitinib against c-myc-amplified high-risk medulloblastoma.Journal of cellular and molecular medicine · 2018Article
- Article
- Genotypes Affecting the Pharmacokinetics of Anticancer Drugs.Clinical pharmacokinetics · 2017Review
- Axitinib in the treatment of renal cell carcinoma: design, development, and place in therapy.Drug design, development and therapy · 2017Review
- Article
- Axitinib in the treatment of renal cell carcinoma: patient selection and perspectives.International journal of nephrology and renovascular disease · 2016Review
- Review
- Axitinib plasma pharmacokinetics and ethnic differences.Investigational new drugs · 2015Review
- Population pharmacokinetic analysis of axitinib in healthy volunteers.British journal of clinical pharmacology · 2014Article
- Axitinib: a review of its safety and efficacy in the treatment of adults with advanced renal cell carcinoma.Clinical Medicine Insights. Oncology · 2013Review
- Clinical pharmacology of axitinib.Clinical pharmacokinetics · 2013Review
- Contribution of OATP1B1 and OATP1B3 to the disposition of sorafenib and sorafenib-glucuronide.Clinical cancer research : an official journal of the American Association for Cancer Research · 2013Article
- Effect of the CYP2C19 genotype on the pharmacokinetics of icotinib in healthy male volunteers.European journal of clinical pharmacology · 2012Article
- Axitinib in Metastatic Renal Cell Carcinoma.Biologics in therapy · 2012Review
Corrections and comments
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Authors and funding
6 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
purposeAxitinib, an orally administered inhibitor of vascular endothelial growth factor 1, 2 and 3, is primarily metabolized by cytochrome P450 (CYP) 3A4/5 but is also a substrate for CYP1A2, CYP2C19, UDP-glucuronosyltransferase (UGT)1A1 and the drug transporters P-glycoprotein (encoded by the ABCB1 gene) and OATP1B1 (encoded by SLC01B1). The potential contribution of polymorphisms in genes encoding these enzymes and transporters to axitinib pharmacokinetic variability was assessed.
methodsA fixed effects meta-analysis was performed using data pooled from 11 healthy volunteer clinical pharmacology trials to investigate the potential association between axitinib exposure and major polymorphisms in these genes following a 5-mg dose of axitinib.
resultsUp to 15 variant alleles were evaluated and up to 315 healthy volunteers per polymorphism were assayed. None of the polymorphisms analysed was a statistically significant predictor of axitinib pharmacokinetic variability. Amongst genotypes and inferred phenotypes, CYP2C19 genotype and the ABCB1 (G2677T/A) polymorphism were the closest to statistical significance in influencing axitinib pharmacokinetic variability after multiple-testing adjustment. However, no enzyme or transporter genotype/inferred phenotype contributed >5% to the overall pharmacokinetic variability of axitinib.
conclusionsNo statistically significant associations between the specific polymorphisms analysed and axitinib plasma exposure were observed, suggesting that genotype- or inferred phenotype-based adjustment of axitinib dose in individual subjects is not warranted.
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