ArticleClinical pharmacokinetics2019
Impact of CYP3A4*22 on Pazopanib Pharmacokinetics in Cancer Patients.
Article in Clinical pharmacokinetics, 2019. 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.
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Who cites it
16 citing papers in PubMed, 1 synthesis or guideline pooled it, 28 citations in OpenAlex.
- CYP3A4*22 Genotype-Guided Dosing of Kinase Inhibitors in Cancer Patients.Clinical pharmacokinetics · 2023Pooled it
- Pharmacogenomic, pharmacokinetic, and safety analysis of CYP3A4/CYP3A5 polymorphisms of midostaurin in patients with acute myeloid leukemia.European journal of clinical pharmacology · 2025Trial
- A Systematic Evaluation of the Dosing Regimens for Approved Targeted Therapies and Immune Checkpoint Inhibitors in Metastatic Renal Cell Carcinoma From a Project OPTIMUS Perspective.Journal of clinical pharmacology · 2025Review
- Ziprasidone population pharmacokinetics and co-medication effects in Chinese patients.Naunyn-Schmiedeberg's archives of pharmacology · 2024Article
- Pazopanib pharmacokinetically guided dose optimization in three cancer patients with gastrointestinal resection.Cancer chemotherapy and pharmacology · 2024Article
- Genetic polymorphisms as predictive biomarkers of adverse events during preoperative chemotherapy in esophageal cancer.Cancer chemotherapy and pharmacology · 2024Article
- Potential association ofPharmacogenomics · 2024Article
- Cannabis Pharmacogenomics: A Path to Personalized Medicine.Current issues in molecular biology · 2023Review
- Therapeutic Drug Monitoring of Tyrosine Kinase Inhibitors in the Treatment of Advanced Renal Cancer.Cancers · 2023Review
- Pharmacogenetics of Anticancer Drugs: Clinical Response and Toxicity.Cancer treatment and research · 2023Article
- The Role of CYP3A in Health and Disease.Biomedicines · 2022Review
- Pharmacogenomics Testing in Phase I Oncology Clinical Trials: Constructive Criticism Is Warranted.Cancers · 2022Review
- Review
- Pharmacogenetic-Pharmacokinetic Interactions in Drug Marketing Authorization Applications via the European Medicines Agency Between 2014 and 2017.Clinical pharmacology and therapeutics · 2020Article
- Imatinib, sunitinib and pazopanib: From flat-fixed dosing towards a pharmacokinetically guided personalized dose.British journal of clinical pharmacology · 2020Review
- Interindividual Variation in CYP3A Activity Influences Lapatinib Bioactivation.Drug metabolism and disposition: the biological fate of chemicals · 2019Article
Corrections and comments
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Authors and funding
14 authors at 7 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
BACKGROUND AND
objectiveAs pazopanib plasma trough concentrations are correlated with treatment outcome, we explored whether single nucleotide polymorphisms in the elimination pathway of pazopanib affect systemic pazopanib concentrations.
methodsThe decreased function alleles CYP3A4 15389 C > T (*22), ABCB1 3435 C >T, ABCG2 421 C >A, and ABCG2 34G >A were analyzed within a recently developed population-pharmacokinetic model.
resultsIncorporation of CYP3A4*22 in the model resulted in a 35% lower clearance for variant carriers (0.18 vs. 0.27 L/h; difference in objective function value: - 9.7; p < 0.005). Simulated median trough concentrations of cancer patients with CYP3A4*22 with 600 mg once daily or 800 mg once daily were 31 and 35 mg/L, respectively. The simulated trough concentrations for the population excluding the CYP3A4*22 carriers after 600 mg once daily or 800 mg once daily were 18 and 20 mg/L, respectively.
conclusionThis analysis shows that CYP3A4*22 heterozygotes have a substantial lower pazopanib clearance and that dose adjustments based on CYP3A4*22 status could be considered.
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