ArticleEuropean journal of clinical pharmacology2022
Role of ADME gene polymorphisms on imatinib disposition: results from a population pharmacokinetic study in chronic myeloid leukaemia.
Article in European journal of clinical pharmacology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers, 2 of them syntheses that pooled it.
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Who cites it
5 citing papers in PubMed, 2 syntheses or guidelines pooled it, 7 citations in OpenAlex.
- Published Population Pharmacokinetic Models of Imatinib Perform Poorly on TDM Data from Pediatric Patients.Targeted oncology · 2025Pooled it
- Predictive performance of population pharmacokinetic models of imatinib in chronic myeloid leukemia patients.Cancer chemotherapy and pharmacology · 2024Pooled it
- Constitutional DNA Polymorphisms Associated with the Plasma Imatinib Concentration in Chronic Myeloid Leukemia Patients.Pharmaceutics · 2024Article
- Population pharmacokinetics and pharmacogenetics analyses of imatinib in Chinese patients with chronic myeloid leukemia in a real-world situation.Cancer chemotherapy and pharmacology · 2023Article
- Personalized Dose of Adjuvant Imatinib in Patients with Gastrointestinal Stromal Tumors: Results from a Population Pharmacokinetic Analysis.Drug design, development and therapy · 2023Article
Corrections and comments
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Authors and funding
12 authors at 2 institutions in 1 country.
Funding
Abstract
purposeImatinib is a substrate of CYP3A4, ABCB1 and ABCG2, and is known to have wide variability in pharmacokinetics (PK). At the same time, a clear relationship between drug levels and response also exists for imatinib in chronic myeloid leukaemia (CML). Therefore, pharmacogenetic-based dosing of imatinib is an attractive proposition. This study aims to characterize the population pharmacokinetics of imatinib in order to identify significant covariates including pharmacogenetic variants.
methodsForty-nine patients with CML were enrolled in the study after being on imatinib for at least 4 consecutive weeks. Steady-state pharmacokinetic sampling was performed either in a sparse (4 samples each, n = 44) or intensive manner (9 samples each, n = 5). An additional pharmacogenetic sample was also collected from all patients. Plasma imatinib levels were estimated using a validated HPLC method. Pharmacogenetic variants were identified using the PharmacoScan array platform. Population pharmacokinetic analysis was carried out using NONMEM v7.2. Seven SNPs within CYP3A4, ABCB1 and ABCG2 genes were evaluated for covariate effect on the clearance of imatinib.
resultsImatinib PK was well characterized using a one-compartment model with zero-order absorption. The clearance and volume of distribution were found to be 10.2 L/h and 389 L respectively. Only SNP rs1128503 of the ABCB1 gene had a small but insignificant effect on imatinib clearance, with a 25% reduction in clearance observed in patients carrying the polymorphism. Twenty-three out of forty-nine patients (47%) carried the polymorphic allele, of whom 17 were heterozygous and six were homozygous.
conclusionOur study conclusively proves that genetic polymorphisms in the CYP3A4 and ABC family of transporters do not have any role in the personalized dosing of imatinib in CML.
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