【作者】 钟安妮； 朱艳； 徐萍； 王清； 蔡骅琳； 向大雄； 姜志平；

【机构】 中南大学湘雅二医院药学部； 中南大学临床药学研究所； 中南大学湘雅医院血液科；

【摘要】 目的:探讨慢性粒细胞白血病患者使用伊马替尼,尤其是在合用伏立康唑等药物时开展治疗药物监测（TDM）的必要性和重要性,并探讨在慢性粒细胞白血病患者中影响伊马替尼与伏立康唑药物浓度的相关因素。方法:描述1例于2018年1月在中南大学湘雅医院确诊慢性粒细胞白血病合并肺部真菌感染并服用伊马替尼与伏立康唑联合治疗的病例,采用超高效液相色谱-串联质谱（UPLC-MS/MS）和二维液相色谱法分别监测伊马替尼和伏立康唑的稳态血浆谷浓度,并根据症状缓解程度、肺部CT和BCR-ABL^IS（P210）定量PCR结果评估患者的临床治疗效果。结果:本例患者联合伊马替尼标准剂量400mg/QD和伏立康唑常规剂量200mg/BID常规治疗三个月后,伊马替尼稳态血浆谷浓度监测显示为589.77ng·ml^-1,伏立康唑血浆谷浓度监测显示为0.03μg·ml^-1,皆显著低于相应的推荐治疗浓度(>1000ng·ml^-1;2.0～5.5μg·ml^-1);并且患者咳嗽症状未得到完全缓解,肺部CT仍显示为双肺感染灶。BCR-ABLIS（P210）定量PCR检测报告显示为17.6%,较确诊时（BCR-ABLIS为14.1%）升高,尚未达早期分子学反应（EMR）。根据上述评估,患者尚未获得良好的治疗效果。结论:本案例提示对服用伊马替尼治疗慢性粒细胞白血病的患者进行治疗药物监测在预测和优化治疗反应上具有重要指导意义,尤其是当伊马替尼与伏立康唑等其他具有潜在药物相互作用而显著相互影响药物浓度时更有意义。但伊马替尼与伏立康唑潜在的药物相互作用对个体间药物浓度差异的影响机制仍需进一步的研究和探讨。更多还原

【Abstract】 Purpose To explore the necessity and significance of therapeutic drug monitoring（TDM） in patients with chronic myeloid leukemia（CML）using imatinib, especially in combination with voriconazole and other drugs, and to investigatethe related factors affectingdrug concentrations of imatinib and voriconazole.Methods We described a case, treated with imatinib and voriconazole for CML complicated with pulmonary infection, who diagnosed at The Xiangya Hospital of Central South University in January 2018.The plasma trough concentrations of imatinib and voriconazole was performed by Ultra Performance Liquid Chromatography-Tandem Mass Spectrometry（UPLC-MS/MS） and two-dimensional liquid chromatography, respectively. And evaluating the clinical treatment efficacybased onthe remission extent of clinical symptoms,pulmonary CT and the result of BCR-ABL^IS（P210）.Results The patient of this caseco-medication of conventional dose of imatinib mesylate 400 mg once daily and voriconazole200 mgtwice daily for three months. The plasma trough concentrationsof imatinib and voriconazole showed 589.76 ng·ml^-1 and 0.03μg·ml^-1, respectively. Both the concentrations of imatinib and voriconazole were significantly lower than the recommended concentrations(>1000 ng·ml^-1; 2.0 ～ 5.5μg·ml^-1). Moreover, the symptoms of cough in the patient had not been completely relieved. Pulmonary CT remained exhibit double pulmonary infection. The BCR-ABLIS（P210） detecting by quantitative PCR after 3 months increased to 17.6%, which higher than at diagnosed（BCR-ABLIS14.1%）, and lacked of EMS（Early molecular responses）.According to the above assessment, the patient had not yet achieved favorable therapeutic effect.Conclusions This case suggests the significance for therapeutic drug monitoringin predicting and optimizing therapeutic responses in patients with CML who treated with imarinib,particularly in the case of variable drug concentrations resulted bythe potential drug interaction between imatinib and other drugs, such as voriconazole.Further prospective studiesinvestigating the mechanismofdrug interactions between imatinib and voriconazole on inter-individual drug concentrations should be performed.更多还原