PMID- 29316372 OWN - NLM STAT- MEDLINE DCOM- 20190520 LR - 20240315 IS - 2045-7634 (Electronic) IS - 2045-7634 (Linking) VI - 7 IP - 2 DP - 2018 Feb TI - Can therapeutic drug monitoring increase the safety of Imatinib in GIST patients? PG - 317-324 LID - 10.1002/cam4.1286 [doi] AB - Imatinib at 400 mg daily is the standard treatment for patients affected with CML and GIST. The intervariability in plasma concentration is very significant. In many reports, a good therapeutic effect is attributed to an adequate concentration of Imatinib. However, few studies have been conducted to investigate the association between plasma concentration and side effects. Besides, no upper concentration limit of Imatinib plasma concentration detection has been established. The correlation of Imatinib trough concentrations (C(min) ) with adverse effects (AEs) was described here. Plasma samples were obtained from patients after 3 months treatment with Imatinib (steady state, n = 122). Liquid chromatography/ tandem mass spectrometry was used to determine the concentration of Imatinib and its metabolite NDI. The incidence of myelosuppression was increased significantly with the increased Imatinib trough plasma concentration. The plasma level of Imatinib and NDI in patients who developed myelosuppression are 1698.3 +/- 598.6 ng/mL and 242.1 ng/mL, respectively, which were significantly higher than those in patients who did not (1327.2 +/- 623.4 ng/mL, P = 1.75 x 10(-4) ; 206.3 ng/mL, P = 0.006). Estimated exposure thresholds of Imatinib and NDI were 1451.6 ng/mL with ROC(AUC) (95%CI) of 0.693 (0.597-0.789) and 207.1 ng/mL with ROC(AUC) (95%CI) of 0.646 (0.546-0.745), respectively. Multivariate regression confirmed the correlation of Imatinib C(min) with myelosuppression. Other side effects such as fluid retention and rash were not found to be correlated with Imatinib concentrations. These results suggest that trough concentration of Imatinib should be taken into consideration to increase the safety of Imatinib therapy in GIST patients. CI - (c) 2017 The Authors. Cancer Medicine published by John Wiley & Sons Ltd. FAU - Zhuang, Wei AU - Zhuang W AD - Institute of Clinical Pharmacology, School of Pharmaceutical Sciences, Sun Yat-Sen University, Guangzhou, 510006, China. FAU - Xie, Jing-Dun AU - Xie JD AD - State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou, 510060, China. FAU - Zhou, Shan AU - Zhou S AD - Institute of Clinical Pharmacology, School of Pharmaceutical Sciences, Sun Yat-Sen University, Guangzhou, 510006, China. FAU - Zhou, Zhi-Wei AU - Zhou ZW AUID- ORCID: 0000-0003-1338-1220 AD - State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou, 510060, China. FAU - Zhou, Yi AU - Zhou Y AD - The first affiliated hospital, Sun Yat-Sen University, Guangzhou, 510080, China. FAU - Sun, Xiao-Wei AU - Sun XW AUID- ORCID: 0000-0003-2321-5955 AD - State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou, 510060, China. FAU - Yuan, Xiu-Hong AU - Yuan XH AD - State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou, 510060, China. FAU - Huang, Min AU - Huang M AD - Institute of Clinical Pharmacology, School of Pharmaceutical Sciences, Sun Yat-Sen University, Guangzhou, 510006, China. FAU - Liu, Si AU - Liu S AD - Institute of Clinical Pharmacology, School of Pharmaceutical Sciences, Sun Yat-Sen University, Guangzhou, 510006, China. FAU - Xin, Shuang AU - Xin S AD - Institute of Clinical Pharmacology, School of Pharmaceutical Sciences, Sun Yat-Sen University, Guangzhou, 510006, China. AD - State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou, 510060, China. FAU - Su, Qi-Biao AU - Su QB AD - College of health science, Guangdong Pharmaceutical University, Guangzhou, Guangzhou, 510006, China. FAU - Qiu, Hai-Bo AU - Qiu HB AD - State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou, 510060, China. FAU - Wang, Xue-Ding AU - Wang XD AUID- ORCID: 0000-0002-3580-9155 AD - Institute of Clinical Pharmacology, School of Pharmaceutical Sciences, Sun Yat-Sen University, Guangzhou, 510006, China. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20180107 PL - United States TA - Cancer Med JT - Cancer medicine JID - 101595310 RN - 0 (Antineoplastic Agents) RN - 8A1O1M485B (Imatinib Mesylate) SB - IM MH - Adolescent MH - Adult MH - Aged MH - Antineoplastic Agents/*adverse effects/pharmacokinetics MH - *Drug Monitoring MH - Female MH - Follow-Up Studies MH - Gastrointestinal Neoplasms/blood/*drug therapy/pathology MH - Gastrointestinal Stromal Tumors/blood/*drug therapy/pathology MH - Humans MH - Imatinib Mesylate/*adverse effects/pharmacokinetics MH - Leukopenia/*chemically induced/diagnosis MH - Male MH - Middle Aged MH - Myelopoiesis/*drug effects MH - Prognosis MH - Tissue Distribution MH - Young Adult PMC - PMC5806097 OTO - NOTNLM OT - GIST OT - Adverse effects OT - Imatinib OT - N-demethyl-Imatinib OT - pharmacokinetics EDAT- 2018/01/10 06:00 MHDA- 2019/05/21 06:00 PMCR- 2018/01/07 CRDT- 2018/01/10 06:00 PHST- 2017/07/02 00:00 [received] PHST- 2017/11/15 00:00 [revised] PHST- 2017/11/18 00:00 [accepted] PHST- 2018/01/10 06:00 [pubmed] PHST- 2019/05/21 06:00 [medline] PHST- 2018/01/10 06:00 [entrez] PHST- 2018/01/07 00:00 [pmc-release] AID - CAM41286 [pii] AID - 10.1002/cam4.1286 [doi] PST - ppublish SO - Cancer Med. 2018 Feb;7(2):317-324. doi: 10.1002/cam4.1286. Epub 2018 Jan 7.