Faculty of Pharmaceutical Sciences, The University of British Columbia, Vancouver, Canada.
Ther Drug Monit. 2012 Feb;34(1):85-97. doi: 10.1097/FTD.0b013e31823cdec9.
Imatinib mesylate is a tyrosine kinase inhibitor used as first-line treatment in Philadelphia chromosome-positive chronic myeloid leukemia (Ph+ CML) and metastatic or unresectable gastrointestinal stromal tumors (GIST). Therapeutic drug monitoring (TDM) for imatinib has been suggested to improve efficacy, assess compliance, and evaluate drug-drug interactions. Imatinib has proven efficacy in improving treatment response and survival in patients with Ph+ CML and GIST. Several analytical methods are available to quantify total plasma imatinib concentrations. A good relationship exists between total imatinib plasma concentrations and pharmacologic response. Clinical evaluation of pharmacologic response to imatinib alone may be insufficient given the long duration of therapy before clinical response in patients with Ph+ CML and GIST. Thus, the authors have used a previously published 9-step decision-making algorithm to evaluate the utility of TDM for imatinib. The suggested trough concentrations for improved complete cytogenetic or major molecular response in patients with Ph+ CML and improved time to progression for patients with GIST are >1000 and >1100 ng/mL, respectively. Imatinib exhibits interindividual pharmacokinetic variability. Increased apparent clearance of imatinib has been observed in chronic phase chronic myeloid leukemia and increased body weight. Decreased apparent clearance has been observed in renal impairment and patients on concomitant medications with potent inhibition of cytochrome P450 3A4. Duration of therapy in patients with Ph+ CML and GIST is lifelong. Based on the available evidence, TDM for imatinib may provide additional information on efficacy, compliance, and safety than clinical evaluation alone. Patients with suboptimal response to treatment, treatment failure, rare adverse events, drug interactions, or suspected nonadherence will attain the greatest benefit from TDM.
甲磺酸伊马替尼是一种酪氨酸激酶抑制剂，用于治疗费城染色体阳性慢性髓性白血病（Ph+ CML）和转移性或不可切除的胃肠道间质瘤（GIST）。有人建议对伊马替尼进行治疗药物监测（TDM），以提高疗效、评估依从性和评估药物相互作用。伊马替尼已被证明可改善 Ph+ CML 和 GIST 患者的治疗反应和生存。有几种分析方法可用于定量测定总血浆伊马替尼浓度。总伊马替尼血浆浓度与药效学反应之间存在良好的关系。由于 Ph+ CML 和 GIST 患者在临床反应之前需要长时间的治疗，因此仅对伊马替尼的药效学反应进行临床评估可能不够。因此，作者使用了先前发表的 9 步决策算法来评估 TDM 对伊马替尼的应用。建议 Ph+ CML 患者的谷浓度为改善完全细胞遗传学或主要分子反应的浓度>1000ng/mL，GIST 患者的谷浓度为改善进展时间的浓度>1100ng/mL。伊马替尼表现出个体间药代动力学的变异性。在慢性期慢性髓性白血病和增加体重的情况下，观察到伊马替尼的表观清除率增加。在肾功能不全和同时服用强效细胞色素 P450 3A4 抑制剂的患者中，观察到伊马替尼的表观清除率降低。Ph+ CML 和 GIST 患者的治疗时间是终身的。基于现有证据，与单独临床评估相比，TDM 可为伊马替尼的疗效、依从性和安全性提供更多信息。对治疗反应不佳、治疗失败、罕见不良反应、药物相互作用或疑似不依从的患者，TDM 将获得最大收益。
