@article{Wang_Jiang_Zeng_Zhu_Cai_Xiang_He_Shi_Zhong_Zhao_et al._2020, title={Effects of Trough Concentration and Solute Carrier Polymorphisms on Imatinib Efficacy in Chinese Patients with Chronic Myeloid Leukemia}, volume={23}, url={https://journals.library.ualberta.ca/jpps/index.php/JPPS/article/view/30559}, DOI={10.18433/jpps30559}, abstractNote={<p><strong>Purpose: </strong>We investigated the relationship between imatinib trough concentrations and genetic polymorphisms with efficacy of imatinib in Chinese patients with chronic myeloid leukemia (CML). <strong>Methods:</strong> There were 171 eligible patients. Peripheral blood samples were collected from 171 eligible patients between 21 and 27 hours after the last imatinib administration. Complete cytogenetic response (CCyR), major molecular response (MMR) and complete molecular response (CMR) were used as metrics for efficacy. Nine single nucleotide polymorphisms in 5 genes, <em>SLC22A4</em> (917 T>C, -248 C>G and -538 C>G), <em>SLC22A5</em> (-945 T>G and -1889 T>C), <em>SLCO1A2</em> (-361 G>A), <em>SLCO1B3</em> (334 T>G and 699 G>A) and <em>ABCG2</em> (421C>A) were selected for genotyping. <strong>Results:</strong> Patients with CCyR achieve higher trough concentrations than those without CCyR (1478.18±659.83 <em>vs</em> 984.89±454.06 ng mL<sup>-1</sup>, <em>p</em><0.001). Patients with MMR and CMR achieve higher trough concentrations than those without MMR and CMR, respectively (1486.40±703.38 <em>vs</em> 1121.17±527.14 ng mL<sup>-1</sup>, <em>p</em>=0.007; 1528.00±709.98 <em>vs</em> 1112.67±518.35 ng mL<sup>-1</sup>, <em>p</em>=0.003, respectively). Carriers of A allele in <em>SLCO1A2</em> -361G>A achieve higher CCyR and MMR rates (<em>p</em>=0.047, OR=4.320, 95% CI: 0.924-20.206; <em>p</em>=0.042, OR=2.825, 95% CI: 1.016-7.853, respectively). Both trough concentrations and <em>SLCO1A2</em> -361G>A genotypes are independent factors affecting imatinib efficacy. The positive and negative predictive values for CCyR are 71.01% and 68.75%, respectively. The positive and negative predictive values for MMR are 62.86% and 69.70%, respectively. <strong>Conclusion:</strong> Imatinib trough concentrations and <em>SLCO1A2 </em>-361G>A genotypes are associated with imatinib efficacy in Chinese patients with CML. <strong>Keywords</strong>: Efficacy, Imatinib, Polymorphisms, Trough concentration</p>}, number={1}, journal={Journal of Pharmacy & Pharmaceutical Sciences}, author={Wang, Qing and Jiang, Zhi-Ping and Zeng, Jing and Zhu, Yan and Cai, Hua-Lin and Xiang, Da-Xiong and He, Qun and Shi, Xiao-Liu and Zhong, An-Ni and Zhao, Xie-Lan and et al.}, year={2020}, month={Jan.}, pages={1–9} }