Next Article in Journal
A Biomedical Investigation of the Hepatoprotective Effect of Radix salviae miltiorrhizae and Network Pharmacology-Based Prediction of the Active Compounds and Molecular Targets
Next Article in Special Issue
Circulating Cell-Free DNA and Circulating Tumor Cells as Prognostic and Predictive Biomarkers in Advanced Non-Small Cell Lung Cancer Patients Treated with First-Line Chemotherapy
Previous Article in Journal
CmMYB19 Over-Expression Improves Aphid Tolerance in Chrysanthemum by Promoting Lignin Synthesis
Previous Article in Special Issue
Predictive and Prognostic Molecular Biomarkers for Response to Neoadjuvant Chemoradiation in Rectal Cancer
Open AccessArticle

Genetic Polymorphisms Contribute to the Individual Variations of Imatinib Mesylate Plasma Levels and Adverse Reactions in Chinese GIST Patients

1
Department of Clinical Pharmacy, School of Pharmacy, Fudan University, Shanghai 201203, China
2
Department of Medical Oncology, Shanghai Cancer Center, Fudan University, Shanghai 200032, China
3
Department of Pathology, Zhongshan Hospital, Fudan University, Shanghai 200032, China
4
Department of General Surgery, Zhongshan Hospital, Fudan University, Shanghai 200032, China
5
Department of Medical Oncology, Zhongshan Hospital, Fudan University, Shanghai 200032, China
*
Authors to whom correspondence should be addressed.
These authors contributed equally to this work.
Academic Editor: William Chi-shing Cho
Int. J. Mol. Sci. 2017, 18(3), 603; https://doi.org/10.3390/ijms18030603
Received: 31 December 2016 / Revised: 27 February 2017 / Accepted: 4 March 2017 / Published: 13 March 2017
Imatinib mesylate (IM) has dramatically improved the outcomes of gastrointestinal stromal tumor (GIST) patients. However, the clinical responses of IM may considerably vary among single individuals. This study aimed to investigate the influences of genetic polymorphisms of drug-metabolizing enzyme (CYP3A4), transporters (ABCB1, ABCG2), and nuclear receptor (Pregnane X Receptor (PXR, encoded by NR1I2)) on IM plasma levels and related adverse reactions in Chinese GIST patients. A total of 68 Chinese GIST patients who have received IM 300–600 mg/day were genotyped for six single nucleotide polymorphisms (SNPs) (CYP3A4 rs2242480; ABCB1 rs1045642; ABCG2 rs2231137; NRI12 rs3814055, rs6785049, rs2276706), and the steady-state IM trough plasma concentrations were measured by a validated HPLC method. There were statistically significant variances in the steady-state IM trough plasma concentrations (from 272.22 to 4365.96 ng/mL). Subjects of GG in rs2242480, T allele carriers in rs1045642 and CC in rs3814055 had significantly higher steady-state IM dose-adjusted trough plasma concentrations. Subjects of CC in rs3814055 had significantly higher incidence rate of edema. The genetic polymorphisms of rs2242480, rs1045642, rs3814055 were significantly associated with IM plasma levels, and the genetic variations of rs3814055 were significantly associated with the incidence rate of edema in Chinese GIST patients. The current results may serve as valuable fundamental knowledge for IM therapy in Chinese GIST patients. View Full-Text
Keywords: imatinib mesylate; gastrointestinal stromal tumor; genetic polymorphisms; plasma levels; adverse reactions; Chinese imatinib mesylate; gastrointestinal stromal tumor; genetic polymorphisms; plasma levels; adverse reactions; Chinese
Show Figures

Graphical abstract

MDPI and ACS Style

Liu, J.; Chen, Z.; Chen, H.; Hou, Y.; Lu, W.; He, J.; Tong, H.; Zhou, Y.; Cai, W. Genetic Polymorphisms Contribute to the Individual Variations of Imatinib Mesylate Plasma Levels and Adverse Reactions in Chinese GIST Patients. Int. J. Mol. Sci. 2017, 18, 603.

Show more citation formats Show less citations formats
Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Article Access Map by Country/Region

1
Search more from Scilit
 
Search
Back to TopTop