ArticleInvestigational new drugs2016
Determination of unbound fraction of pazopanib in vitro and in cancer patients reveals albumin as the main binding site.
Article in Investigational new drugs, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers, 1 of them a synthesis that pooled it.
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Who cites it
13 citing papers in PubMed, 1 synthesis or guideline pooled it, 29 citations in OpenAlex.
- Pazopanib: Evidence review and clinical practice in the management of advanced renal cell carcinoma.BMC pharmacology & toxicology · 2018Pooled it
- A Review of FDA-Approved Multi-Target Angiogenesis Drugs for Brain Tumor Therapy.International journal of molecular sciences · 2025Review
- Physiologically-based pharmacokinetic models versus allometric scaling for prediction of tyrosine-kinase inhibitor exposure from adults to children.Cancer chemotherapy and pharmacology · 2024Article
- Combination therapy with pazopanib and tivantinib modulates VEGF and c-MET levels in refractory advanced solid tumors.Investigational new drugs · 2021Article
- HPLC-MS/MS coupled with equilibrium dialysis method for quantification of free drug concentration of pazopanib in plasma.Heliyon · 2020Article
- Imatinib, sunitinib and pazopanib: From flat-fixed dosing towards a pharmacokinetically guided personalized dose.British journal of clinical pharmacology · 2020Review
- Effect of tyrosine kinase inhibitors on renal handling of creatinine by MATE1.Scientific reports · 2018Article
- Pazopanib-related tumor lysis syndrome in metastatic clear cell renal cell carcinoma: a case report.Investigational new drugs · 2018Article
- Real World Experience of Drug Induced Liver Injury in Patients Undergoing Chemotherapy.Journal of clinical gastroenterology and hepatology · 2018Article
- Tyrosine Kinase Inhibitor Pazopanib Inhibits Platelet Procoagulant Activity in Renal Cell Carcinoma Patients.Frontiers in cardiovascular medicine · 2018Article
- Clinical Pharmacokinetics and Pharmacodynamics of Pazopanib: Towards Optimized Dosing.Clinical pharmacokinetics · 2017Review
- PharmGKB summary: pazopanib pathway, pharmacokinetics.Pharmacogenetics and genomics · 2017Review
- Pazopanib Reduces Phosphorylated Tau Levels and Alters Astrocytes in a Mouse Model of Tauopathy.Journal of Alzheimer's disease : JAD · 2017Article
Corrections and comments
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Authors and funding
8 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
introductionPazopanib exhibits wide inter-patient pharmacokinetic variability which may contribute to differences in treatment outcome. Unbound drug concentrations are believed to be more relevant to pharmacological responses than total concentrations. Thus it is desirable to evaluate pazopanib binding on plasma proteins and different factors potentially affecting this process.
methodsAn equilibrium dialysis method coupled with UPLC-MS/MS assay has been optimized and validated for the determination of pazopanib unbound fraction (fu%) in human plasma. Pazopanib binding in the plasma of healthy volunteers and in isolated protein solutions was investigated. The unbound fraction was determined for 24 cancer patients treated daily with pazopanib.
resultsWe found that pazopanib was extensively bound in human plasma (>99.9 %) with a mean fu% value of 0.0106 ± 0.0013 % at 40 μg/mL. Protein binding was concentration independent over a clinically relevant range of concentrations. In isolated protein solutions, pazopanib at 40 μg/mL was mainly bound to albumin (40 g/L) and to a lesser extent to α1-acid glycoprotein (1 g/L) and low density lipoproteins (1.2 g/L), with a mean fu% of 0.0073 ± 0.0022 %, 0.992 ± 0.44 % and 7.4 ± 1.7 % respectively. Inter-patient variability (CV%) of fu% in cancer patients was limited (27.2 %). A correlation was observed between individual unbound fraction values and albuminemia.
conclusionsPazopanib exhibits extensive binding to plasma proteins in human plasma. Variable albumin concentrations, frequently observed in cancer patients, may affect pazopanib unbound fraction with implications for inter-patient variability in drug efficacy and toxicity.
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