Effects of Trough Concentration and Solute Carrier Polymorphisms on Imatinib Efficacy in Chinese Patients with Chronic Myeloid Leukemia

Authors

  • Qing Wang Department of Pharmacy, the Second Xiangya Hospital, Central South University; Institute of Clinical Pharmacy, Central South University
  • Zhi-Ping Jiang Laboratory of Clinical Pharmacology, Department of Hematology, Xiangya Hospital, Central South University
  • Jing Zeng Department of Education and Research, Ningbo Medical Center, Li Huili Eastern Hospital
  • Yan Zhu Department of Pharmacy, the Second Xiangya Hospital, Central South University; Institute of Clinical Pharmacy, Central South University
  • Hua-Lin Cai Department of Pharmacy, the Second Xiangya Hospital, Central South University; Institute of Clinical Pharmacy, Central South University
  • Da-Xiong Xiang Department of Pharmacy, the Second Xiangya Hospital, Central South University; Institute of Clinical Pharmacy, Central South University
  • Qun He Laboratory of Clinical Pharmacology, Department of Hematology, Xiangya Hospital, Central South University
  • Xiao-Liu Shi Laboratory of Clinical Diagnosis and Research, Department of Medical Genetics, the Second Xiangya Hospital of Central South University
  • An-Ni Zhong Department of Pharmacy, the Second Xiangya Hospital, Central South University; Institute of Clinical Pharmacy, Central South University
  • Xie-Lan Zhao Laboratory of Clinical Pharmacology, Department of Hematology, Xiangya Hospital, Central South University
  • Ping Xu Department of Pharmacy, the Second Xiangya Hospital, Central South University; Institute of Clinical Pharmacy, Central South University

DOI:

https://doi.org/10.18433/jpps30559

Abstract

Purpose: We investigated the relationship between imatinib trough concentrations and genetic polymorphisms with efficacy of imatinib in Chinese patients with chronic myeloid leukemia (CML). Methods: 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, SLC22A4 (917 T>C, -248 C>G and -538 C>G), SLC22A5 (-945 T>G and -1889 T>C), SLCO1A2 (-361 G>A), SLCO1B3 (334 T>G and 699 G>A) and ABCG2 (421C>A) were selected for genotyping. Results: Patients with CCyR achieve higher trough concentrations than those without CCyR (1478.18±659.83 vs 984.89±454.06 ng mL-1, p<0.001). Patients with MMR and CMR achieve higher trough concentrations than those without MMR and CMR, respectively (1486.40±703.38 vs 1121.17±527.14 ng mL-1, p=0.007; 1528.00±709.98 vs 1112.67±518.35 ng mL-1, p=0.003, respectively). Carriers of A allele in SLCO1A2 -361G>A achieve higher CCyR and MMR rates (p=0.047, OR=4.320, 95% CI: 0.924-20.206; p=0.042, OR=2.825, 95% CI: 1.016-7.853, respectively). Both trough concentrations and SLCO1A2 -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. Conclusion: Imatinib trough concentrations and SLCO1A2 -361G>A genotypes are associated with imatinib efficacy in Chinese patients with CML. Keywords: Efficacy, Imatinib, Polymorphisms, Trough concentration

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Published

2020-01-17

How to Cite

Wang, Q., Jiang, Z.-P., Zeng, J., Zhu, Y., Cai, H.-L., Xiang, D.-X., He, Q., Shi, X.-L., Zhong, A.-N., Zhao, X.-L., & Xu, P. (2020). Effects of Trough Concentration and Solute Carrier Polymorphisms on Imatinib Efficacy in Chinese Patients with Chronic Myeloid Leukemia. Journal of Pharmacy & Pharmaceutical Sciences, 23(1), 1-9. https://doi.org/10.18433/jpps30559

Issue

Section

Clinical Pharmacology and Therapeutics