目的 探讨不同剂量替考拉宁在重症感染患者血药谷浓度(ρmin)的分布特征及影响因素。方法 回顾性分析我院2018年12月~2020年5月使用替考拉宁的238例重症感染患者,按不同给药剂量分为标准剂量组(GS)400 mg,中剂量组(GM)600 mg和高剂量组(GH)800 mg,采用超高效液相色谱-串联质谱联用法(UHPLC-MS/MS)测定替考拉宁ρmin,采用多元线性回归分析以及逐步回归分析法分析替考拉宁ρmin的影响因素。结果 本研究中共监测了238重症感染患者的367个血样,替考拉宁平均ρmin为(16.06±11.81)μg·mL-1,只有65.4%的在治疗窗范围内。替考拉宁ρmin的值按从GS组、GM组和GH组的顺序显著增加[(12.52±8.41)μg·mL-1、(16.46±11.74)μg·mL-1和(20.59±14.49)μg·mL-1],P＜0.05。3组浓度达标率分别为48.39%,68.32%和 84.15%,差异有统计学意义(P<0.001);当替考拉宁谷浓度升高时,肾毒性、肝毒性和血小板减少不良反应发生率均有升高趋势,但是3个剂量组患者药物不良反应发生率无明显统计学差异(P>0.05)。多元线性回归分析结果提示,给药剂量、肾小球滤过率及白蛋白水平为影响重症感染患者替考拉宁血药浓度的主要因素。结论 替考拉宁在重症感染患者中采用常规剂量给药多数患者浓度不达标,应给予足够负荷剂量的替考拉宁,以保证替考拉宁ρmin在治疗窗范围内,从而提高替考拉宁治疗的有效性。给药剂量、肾小球清除率及白蛋白水平对替考拉宁ρmin有影响。
Abstract
OBJECTIVE To explore the characteristics of the serum trough concentration (ρmin) and influencing factors of teicoplanin in different dosages patients with severe infections. METHODS Patients (238 cases) who took teicoplanin from December 2018 to May 2020 were enrolled in a retrospective study and divided into standard-dose group (GS) 400 mg, medium-dose group (GM) 600 mg and high-dose group (GH) 800 mg. The serum ρmin of teicoplanin was measured by ultra performance liquid chromatography tandem mass spectrometry (UHPLC-MS/MS) method. Influencing factors of teicoplanin was analyzed by multiple linear regression and stepwise regression. RESULTS Totally 367 samples were collected from 238 patients. The average concentration of teicoplanin ρmin was (16.06±11.81) μg·mL-1 and only 65.4% of teicoplanin ρmin were in the range of therapeutic window. The ρmin of teicoplanin was significantly increased in the order of GS group, GM group and GH group [(12.52±8.41), (16.46±11.74) μg·mL-1 vs. (20.59±14.49) μg·mL-1], P<0.05. The rate of effective serum trough concentration was 48.39%, 68.32% and 84.15% respectively, with statistically significant difference (P<0.001). There was no significant difference in the incidence of adverse drug reactions (P>0.05). Multiple linear regression analysis showed that the dosage, glomerular clearance rate and albumin level were the main factors influencing teicoplanin concentration in patients with severe infection. CONCLUSION The ρmin of teicoplanin in patients with severe infection has great individual differences. Most of the patients are not up to the standard with conventional dosage. The dosage of teicoplanin, glomerular clearance rate and albumin level have influence on the ρmin of teicoplanin. When teicoplanin is used in patients with severe infection, sufficient loading dose of teicoplanin should be given to ensure that the ρmin of teicoplanin is within the treatment window, to improve the effectiveness of teicoplanin treatment.
关键词
替考拉宁 /
重症感染患者 /
治疗药物监测 /
谷浓度 /
影响因素
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Key words
teicoplanin /
severe infection /
therapeutic drug monitoring /
trough concentration /
influencing factor
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中图分类号：
R969.3
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参考文献
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脚注
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基金
国家重点研发计划项目资助(2020YFC2008304)
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