目的 结合治疗药物监测及GPIIb/IIIa基因多态性检测,分析利奈唑胺谷浓度影响因素及其致血小板减少影响因素,为利奈唑胺使用患者个体化治疗提供理论支持。方法 选取我院30例利奈唑胺使用患者,超高效液相串联质谱法(ultra performance liquid chromatography tandem mass spectrometry, UPLC-MS/MS)检测利奈唑胺谷浓度,测序检测GPIIb/IIIa基因多态性。t检验、卡方检验、线性回归等分析利奈唑胺谷浓度、血小板减少影响因素,多重线性回归分析血小板变化率影响因素。结果 影响利奈唑胺谷浓度的主要因素为用药剂量和估算肾小球滤过率(estimated glomerular filtration rate, eGFR),建议肾功能不全患者加强对利奈唑胺谷浓度的监测。利奈唑胺致血小板减少与患者性别、eGFR、用药剂量及利奈唑胺谷浓度显著相关,以性别、eGFR、用药时间、GPIIb/IIIa基因型CC为自变量建立的多重线性回归方程具有统计学意义,可以解释32.5%的血小板减少原因。结论 性别、eGFR、利奈唑胺谷浓度、GPIIb/IIIa基因多态性、用药时间和用药剂量与利奈唑胺致血小板减少存在相关性,可以通过多重线性回归方程预测血小板减少的发生,指导利奈唑胺个体化治疗。
Abstract
OBJECTIVE To analyze the influencing factors of linezolid trough concentration and linezolid induced thrombocytopenia and provide theoretical support for individual treatment of patients using linezolid. METHODS Thirty cases of patients using linezolid in our hospital were selected. An ultra performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) assay was conducted to detect linezolid trough concentration. GPIIb/IIIa gene polymorphism was determined by genetic sequencing. t test, chi-square test and linear regression were applied to analyze the influence factors of linezolid trough concentration and thrombocytopenia. With multiple linear regressions, platelet change rate was estimated. RESULTS Administration dosage and estimated glomerular filtration rate (eGFR) were primary determinants of linezolid trough concentration. Patients with renal insufficiency were suggested to enhance the monitoring of linezolid trough concentration. Linezolid induced thrombocytopenia was significantly related to gender, eGFR, administration dosage and trough concentration of linezolid. The multiple linear regression equation with sex, eGFR, administration duration, GPIIb/IIIa genotype CC as independent variables was statistically significant, which could explain 32.5% of thrombocytopenia. CONCLUSION Gender, eGFR, Linezolid though concentration, GPIIb/IIIa gene polymorphism, administration duration and dosage are correlated with linezolid induced thrombocytopenia. Multiple linear regression equation could be used to predict the occurrence of thrombocytopenia and guide the individualized treatment of linezolid.
关键词
利奈唑胺 /
超高效液相串联质谱法 /
治疗药物监测 /
GPIIb/IIIa /
基因多态性
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Key words
linezolid /
UPLC-MS/MS /
therapeutic drug monitoring /
GPIIb/IIIa /
gene polymorphism
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中图分类号：
R969.1
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基金
国家自然科学基金项目资助(81903719);中央高校基本科研业务费专项资金项目资助(3332019116);北京药学会2018年临床药学研究项目资助(2018-01-13);中日友好医院 2019 年院级科研基金资助课题项目资助(2018-2-QN-29)
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