Factors Influencing the Steady-State Plasma Concentration of Imatinib Mesylate in Patients With Gastrointestinal Stromal Tumors and Chronic Myeloid Leukemia

Yan Chen; Xiuhua Dong; QiuJu Wang; ZhiXi Liu; XinWei Dong; Sanjun Shi; HongTao Xiao

doi:10.3389/fphar.2020.569843

Factors Influencing the Steady-State Plasma Concentration of Imatinib Mesylate in Patients With Gastrointestinal Stromal Tumors and Chronic Myeloid Leukemia

Front Pharmacol. 2020 Nov 25:11:569843. doi: 10.3389/fphar.2020.569843. eCollection 2020.

Authors

Yan Chen¹, Xiuhua Dong², QiuJu Wang³, ZhiXi Liu¹, XinWei Dong⁴, Sanjun Shi⁵, HongTao Xiao^{1

6}

Affiliations

¹ Department of Clinical Pharmacy, Sichuan Cancer Hospital and Institute, Sichuan Cancer Center, School of Medicine, University of Electronic Science and Technology of China, Chengdu, China.
² Department of Stomatology, The 1st Affiliated Hospital of Chengdu Medical College, Chengdu, China.
³ Department of Clinical Laboratory, Sichuan Cancer Hospital and Institute, Sichuan Cancer Center, School of Medicine, University of Electronic Science and Technology of China, Chengdu, China.
⁴ Department of Pharmacy, Chengdu Medical College, Chengdu, China.
⁵ School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, China.
⁶ Personalized Drug Therapy Key Laboratory of Sichuan Province, Chengdu, China.

Abstract

Imatinib mesylate (IM) is the standard treatment for advanced, metastatic gastrointestinal stromal tumors (GISTs) and chronic myeloid leukemia (CML) with a fixed daily standard dosage via the oral route. Interindividual and intraindividual variability in plasma concentrations have been closely linked to the efficacy of IM therapy. Therefore, this review identifies and describes the key factors influencing the plasma concentration of IM in patients with GISTs and CML. We used the following keywords to search the PubMed, EMBASE, Ovid, Wangfang, and CNKI databases to identify published reports: IM, plasma concentration, GISTs, CML, drug combination/interaction, pathology, and genotype/genetic polymorphism, either alone or in combination. This literature review revealed that only 10 countries have reported the mean concentrations of IM in GISTs or CML patients and the clinical outcomes in different ethnic groups and populations. There were totally 24 different gene polymorphisms, which were examined for any potential influence on the steady-state plasma concentration of IM. As a result, some genotype locus made discrepant conclusion. Herein, the more sample capacity, multicenter, long-term study was worthy to carry out. Eleven reports were enumerated on clinical drug interactions with IM, while there is not sufficient information on the pharmacokinetic parameters altered by drug combinations with IM that could help in investigating the actual drug interactions. The drug interaction with IM should be paid more attention in the future research.

Keywords: chronic myeloid leukemia; gastrointestinal stromal tumor; imatinib; influence factors; therapeutic drug monitoring.