Association analysis of SNPs present in plasma with adverse events and population pharmacokinetics in Chinese sunitinib treated patients with renal cell carcinoma
BACKGROUND: Sunitinib is a tyrosine kinase inhibitor with effective therapeutic outcomes in patients with renal-cell carcinoma. The study were to analyze the association of single-nucleotide polymorphisms present in cell-free DNA and pharmacokinetics with sunitinib treatment-emergent adverse events in Chinese patients with renal-cell carcinoma.
MATERIALS AND METHODS: We genotyped 8 keys SNPs in 6 candidate genes. The plasma concentrations of sunitinib and N-desethyl sunitinib were measured using a high performance liquid chromatography-tandam mass spectrometry method. Correlations between the single-nucleotide polymorphisms and adverse events were investigated by univariate and multivariate logistic regression and we quantitatively evaluated the effect of single-nucleotide polymorphisms on the pharmacokinetics of sunitinib by using a population PK model.
RESULTS: Necessary dose reductions of sunitinib were significantly correlated with SNP rs1933437 in FLT3. A higher severity of AEs were collected with SNP rs2032582 in ABCB1 and rs1800812 in PDGFRα. Thrombocytopenia was collected with rs1800812 in PDGFRα. Our study provides a population PK model of sunitinib with the ABCB1 genotype as a predictive covariate for apparent oral clearance.
CONCLUSIONS: Our study preliminarily confirmed the hypothesis that the pharmacokinetics of sunitinib is affected by the SNPs of enzyme in Chinese renal-cell carcinoma patients, and this affects the different distribution and severity of adverse events of sunitinib.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2018 |
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| Erschienen: |
2018 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:9 |
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| Enthalten in: |
Oncotarget - 9(2018), 18 vom: 06. März, Seite 14109-14123 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Zhang, Yuanyuan [VerfasserIn] |
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| Links: |
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| Themen: |
Cell-free DNA |
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| Anmerkungen: |
Date Revised 16.03.2022 published: Electronic-eCollection Citation Status PubMed-not-MEDLINE |
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| doi: |
10.18632/oncotarget.23881 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM282370897 |
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| 245 | 1 | 0 | |a Association analysis of SNPs present in plasma with adverse events and population pharmacokinetics in Chinese sunitinib treated patients with renal cell carcinoma |
| 264 | 1 | |c 2018 | |
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| 500 | |a published: Electronic-eCollection | ||
| 500 | |a Citation Status PubMed-not-MEDLINE | ||
| 520 | |a BACKGROUND: Sunitinib is a tyrosine kinase inhibitor with effective therapeutic outcomes in patients with renal-cell carcinoma. The study were to analyze the association of single-nucleotide polymorphisms present in cell-free DNA and pharmacokinetics with sunitinib treatment-emergent adverse events in Chinese patients with renal-cell carcinoma | ||
| 520 | |a MATERIALS AND METHODS: We genotyped 8 keys SNPs in 6 candidate genes. The plasma concentrations of sunitinib and N-desethyl sunitinib were measured using a high performance liquid chromatography-tandam mass spectrometry method. Correlations between the single-nucleotide polymorphisms and adverse events were investigated by univariate and multivariate logistic regression and we quantitatively evaluated the effect of single-nucleotide polymorphisms on the pharmacokinetics of sunitinib by using a population PK model | ||
| 520 | |a RESULTS: Necessary dose reductions of sunitinib were significantly correlated with SNP rs1933437 in FLT3. A higher severity of AEs were collected with SNP rs2032582 in ABCB1 and rs1800812 in PDGFRα. Thrombocytopenia was collected with rs1800812 in PDGFRα. Our study provides a population PK model of sunitinib with the ABCB1 genotype as a predictive covariate for apparent oral clearance | ||
| 520 | |a CONCLUSIONS: Our study preliminarily confirmed the hypothesis that the pharmacokinetics of sunitinib is affected by the SNPs of enzyme in Chinese renal-cell carcinoma patients, and this affects the different distribution and severity of adverse events of sunitinib | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a cell-free DNA | |
| 650 | 4 | |a pharmacokinetics | |
| 650 | 4 | |a renal-cell carcinoma | |
| 650 | 4 | |a single-nucleotide polymorphisms | |
| 650 | 4 | |a sunitinib | |
| 700 | 1 | |a Mai, Haixing |e verfasserin |4 aut | |
| 700 | 1 | |a Guo, Gang |e verfasserin |4 aut | |
| 700 | 1 | |a Bi, Guofang |e verfasserin |4 aut | |
| 700 | 1 | |a Hao, Guangtao |e verfasserin |4 aut | |
| 700 | 1 | |a Li, Yuanyuan |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Xiaofang |e verfasserin |4 aut | |
| 700 | 1 | |a Cheng, Longmei |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Jing |e verfasserin |4 aut | |
| 700 | 1 | |a Dong, Ruihua |e verfasserin |4 aut | |
| 700 | 1 | |a Liu, Zeyuan |e verfasserin |4 aut | |
| 700 | 1 | |a Chen, Lijun |e verfasserin |4 aut | |
| 700 | 1 | |a Qu, Hengyan |e verfasserin |4 aut | |
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