Population pharmacokinetics and pharmacogenetics analyses of imatinib in Chinese patients with chronic myeloid leukemia in a real-world situation

He, Shiyu; Shao, Qianhang; Zhao, Jinxia; Bian, Jialu; Zhao, Yinyu; Hao, Xu; Li, Yuanyuan; Hu, Lei; Liu, Boyu; He, Huan; Huang, Lin; Jiang, Qian

doi:10.1007/s00280-023-04581-0

Cited by 4 publications

(3 citation statements)

References 39 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…As already mentioned, very few studies have previously been performed to identify genetic variants potentially associated with ima[C]min. These studies were conducted on a small number of patients using the candidate-gene approach [ 16 , 17 , 18 , 19 ]. However, the candidate-gene approach presents several limitations: the choice of candidate genes may be inappropriate, the causative genes may be either upstream or downstream in signaling pathways, the selected SNPs may provide incomplete coverage of the gene, most studies were underpowered, and importantly, these studies relied on prior hypotheses, which precludes the discovery of genetic variants in previously unknown pathways.…”

Section: Discussionmentioning

confidence: 99%

“…We also did not find any SNPs that we and others had previously found to be associated with the molecular response [ 13 ], with the exception of CYP4F3, which was reported in 2004 but has never been retested [ 25 ]. Furthermore, recently published studies focusing on genes selected for their previously claimed pharmacological functions (such as CYP3A4, CYP3A5, ABCB1, ABCG2, and SCL22A1) have failed to demonstrate an association with imatinib clearance [ 16 ], whereas the hemoglobin concentration and estimated glomerular filtration rate did [ 18 ]. Thus, the question has been raised as to whether measuring plasma imatinib trough levels is an appropriate means to predict the response of CML patients [ 26 ].…”

Section: Discussionmentioning

confidence: 99%

“…Although we and others have focused on DNA polymorphisms associated with the response to imatinib [ 13 , 14 , 15 ], very few genetic studies have been performed to explore associations between SNPs and imatinib plasma concentrations [ 16 , 17 , 18 , 19 ], with none in relation to RNA expression. Moreover, the SNP studies were limited to the candidate-gene approach, which has several limitations, such as a reliance on a priori hypotheses and frequent arbitrary choices, which have been largely detailed [ 20 , 21 ].…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Constitutional DNA Polymorphisms Associated with the Plasma Imatinib Concentration in Chronic Myeloid Leukemia Patients

Bruzzoni-Giovanelli,

Zouali,

Sahbatou

et al. 2024

Pharmaceutics

View full text Add to dashboard Cite

The tyrosine kinase Inhibitor (TKI) imatinib is approved for the treatment of the chronic phase of chronic myeloid leukemia (CP-CML). Pharmacokinetic studies have highlighted the importance of inter-patient variability on imatinib plasma trough concentrations (ima[C]min). In the OPTIM-imatinib trial, we demonstrated that therapeutic drug monitoring (TDM) is able to improve the molecular response of CP-CML patients treated with imatinib. Here, we analyzed the constitutional exomes and RNAseq data of these patients. We performed an association analysis between the constitutional genetic variants of the patients and their ima[C]min, measured after 12 weeks of treatment with 400 mg once daily. Using linear regression, we identified 50 SNPs that showed excess heterozygosity depending on the ima[C]min. Ten SNPs were from non-coding sequences, and among the 40 remaining, 30 (from 25 genes) could be split into two categories. The first group of 16 SNPs concerns genes encoding extracellular matrix, cell junction, and membrane proteins. Coincidentally, cell adhesion proteins were also identified by RNA-seq as being overexpressed in patients with high ima[C]min. The other group of 14 SNPs were from genes encoding proteins involved in transcription/translation. Although most of the SNPs are intronic variants (28), we also identified missense (3), synonymous (4), 5′/3′ (2), splicing (1), and upstream (4) variants. A haplotype analysis of four genes showed a significant association with high ima[C]min. None of the SNPs were significantly associated with the response. In conclusion, we identified a number of ima[C]min-associated SNPs, most of which correspond to genes encoding proteins that could play a role in the diffusion and transit of imatinib through membranes or epithelial barriers.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Constitutional DNA Polymorphisms Associated with the Plasma Imatinib Concentration in Chronic Myeloid Leukemia Patients

Bruzzoni-Giovanelli,

Zouali,

Sahbatou

et al. 2024

Pharmaceutics

View full text Add to dashboard Cite

show abstract

Understanding the impact of ABCG2 polymorphisms on drug pharmacokinetics: focus on rosuvastatin and allopurinol

Kasten,

Cascorbi

2024

Expert Opinion on Drug Metabolism & Toxicology

View full text Add to dashboard Cite

The Dosage Recommendation of Cyclosporin in Children with Hemophagocytic Lymphohistiocytosis based on Population Pharmacokinetic Model

Yang,

Li,

et al. 2023

CPD

View full text Add to dashboard Cite

Objectives:: Cyclosporin is one of the therapeutic regimens for hemophagocytic lymphohistiocytosis (HLH); however, the optimal dosage of cyclosporine in children with HLH is unknown. It has been found that piperacillin-tazobactam affects the cyclosporine pharmacokinetic process in pediatric HLH patients. Thus, the purpose of the present study was to recommend cyclosporin dosage for pediatric HLH with and without piperacillin- tazobactam. Methods:: A previously established cyclosporine population pharmacokinetic model for pediatric HLH patients has been used in this study to recommend optimal dosage based on Monte Carlo simulation. The pediatric HLH patients have been included in eight weight groups (5, 10, 20, 30, 40, 50, 60, 70 kg) for sixteen dosages (1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16 mg/kg), split into one dose or two doses. Results:: The optimal cyclosporin dosages for children having HLH without piperacillin-tazobactam have been found to be 15, 13, 12, 11, 10, and 9 mg/kg, split into two doses for weights of 5-7, 7-10, 10-20, 20-28, 28-45, and 45-70 kg, respectively. For children with HLH, optimal cyclosporin dosages with piperacillin-tazobactam have been found to be 8 and 7 mg/kg, split into two doses for weights of 5-20 and 20-70 kg, respectively. Conclusion: It is the first time that the cyclosporin dosage regimens for HLH in children have been developed based on Monte Carlo simulation, and the initial dosage optimizations of cyclosporine in pediatric HLH patients have been recommended.

show abstract

Population pharmacokinetics and pharmacogenetics analyses of imatinib in Chinese patients with chronic myeloid leukemia in a real-world situation

Cited by 4 publications

References 39 publications

Constitutional DNA Polymorphisms Associated with the Plasma Imatinib Concentration in Chronic Myeloid Leukemia Patients

Constitutional DNA Polymorphisms Associated with the Plasma Imatinib Concentration in Chronic Myeloid Leukemia Patients

Understanding the impact of ABCG2 polymorphisms on drug pharmacokinetics: focus on rosuvastatin and allopurinol

The Dosage Recommendation of Cyclosporin in Children with Hemophagocytic Lymphohistiocytosis based on Population Pharmacokinetic Model

Contact Info

Product

Resources

About