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| 利奈唑胺谷浓度在利福平耐药结核病患者中的监测与应用 |
| Monitoring and application of linezolid trough concentration in patients with Rifampicin-resistant tuberculosis |
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| DOI：10.3969/j.issn.1007-8134.2023.04.08 |
| 中文关键词: 利奈唑胺 谷浓度 耐药结核 监测与应用 疗效 不良反应 参考范围 个体化治疗 |
| 英文关键词: linezolid trough concentration drug-resistant tuberculosis monitoring and application efficacy adverse drug reaction reference range individualized therapy |
| 基金项目:云南省高层次卫生健康技术人才培养专项经费资助项目（H-2018018） |
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| 中文摘要: |
| 目的?探讨利奈唑胺谷浓度在利福平耐药结核病患者中的有效参考浓度范围，并分析利奈唑胺谷浓度的影响因素及利奈唑胺不良反应发生的影响因素，为其在利福平耐药结核病患者个体化治疗中的应用提供理论依据。方法?选取我院使用利奈唑胺治疗耐药肺结核的94例次患者的血液样本，使用全自动二维液相色谱法测定利奈唑胺谷浓度，构建多元线性回归模型分析利奈唑胺谷浓度的影响因素。应用多元Logistic回归模型探讨药物不良反应发生的影响因素。对利奈唑胺谷浓度进行描述性统计，结合疗效及不良反应发生情况初步确定利奈唑胺谷浓度的有效参考范围。结果?患者血利奈唑胺谷浓度在0.12～6.62 mg/L之间，平均血药谷浓度值为1.24 mg/L。用药剂量及体质量指数是影响利奈唑胺谷浓度的重要因素（P=0.000，P=0.033），得到下列回归方程：Y（谷浓度）= -0.029+5.058X1（用药剂量）-0.079X2（BMI）（R2=0.467）。谷浓度和肌酐清除率与药物不良反应的发生有关联，即每增加1个单位的谷浓度，不良反应的发生风险增加为之前的6.519倍，每增加1个单位肌酐清除率，不良反应的发生风险降低为之前0.957倍。结论?结合疗效相关性及不良反应发生情况，建议利奈唑胺治疗耐药结核的血药谷浓度的推荐参考范围在0.25～2.00 mg/L之间。可通过建立的多元线性回归方程预测利奈唑胺谷浓度，指导利奈唑胺个体化治疗。 |
| 英文摘要: |
| Objective To investigate the effective reference concentration range of linezolid trough concentration in patients with drug-resistant tuberculosis, and analyze the influencing factors of linezolid trough concentration and the influencing factors of linezolid adverse reactions, so as to provide theoretical basis for individual treatment of linezolid. Methods?Ninety-four patients with drug-resistant tuberculosis using linezolid in our hospital were selected. Automatic 2-dimensional liquid chromatography (2D-HPLC) was used to determine linezolid trough concentration, and multiple linear regression model was established to analyze the influencing factors of linezolid trough concentration. Multiple Logistic regression model was used to explore the influencing factors of adverse drug reactions. Descriptive statistics of linezolid trough concentration were performed, and the effective reference range of linezolid trough concentration was initially determined based on the efficacy and adverse reactions. Results?The linezolid trough concentration of the patients ranged from 0.12 to 6.62 mg/L, and the average concentration was 1.24 mg/L. Dose(P＜0.001) and body mass index (BMI) (P=0.033) were important factors affecting linezolid trough concentration. The regression equation was obtained as following: Y (trough concentration) =-0.029+5.058X1 (dose)-0.079X2 (BMI) (R2=0.467). Trough concentration and creatinine clearance rate (Ccr) were associated with the adverse reactions. The risk of adverse reactions increased by 6.519 times for each unit increased in trough concentration, and decreased by 0.957 times for each unit increased in Ccr. Conclusions?Considering the correlation of efficacy and the adverse reactions, it is suggested that the recommended reference range of linezolid trough concentration is between 0.25 and 2.00 mg/L. The established multiple linear regression equation can be used to predict the trough concentration of linezolid, and guide the individual treatment of linezolid. |
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