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[摘要]
目的 通过分析重症患者伏立康唑血药谷浓度的变化,探讨重症患者最优化的伏立康唑给药方案。方法 采用回顾性分析研究,选择2014年12月-2016年12月入住南京大学医学院附属鼓楼医院重症医学科使用伏立康唑并监测伏立康唑血药谷浓度的重症患者,从性别、年龄、体重、APACHE2评分、剂量、总胆红素、白蛋白与浓度相关性,浓度分布情况、质子泵抑制剂对伏立康唑血药谷浓度的影响及疗效等进行统计分析。结果 共纳入99例患者,监测150例次伏立康唑血药谷浓度,其中仅76.00%(114/150)达目标范围1~5.5 mg/L,<1 mg/L占13.33%(17/150),>5.5 mg/L占12.67%(19/150);高龄患者(年龄 ≥ 60岁)伏立康唑血药谷浓度与中青年组相比有统计学差异(P<0.05),多重线性回归分析显示,除年龄外(P=0.000),性别、体重、体重标准化剂量、APACHE2评分、总胆红素及白蛋白对血药谷浓度的影响均无统计学意义;是否使用质子泵抑制剂与伏立康唑血药谷浓度无显著性差异(P=0.165),联用泮托拉唑患者血药浓度呈上升趋势(P=0.054),联用泮托拉唑与艾司奥美拉唑相比伏立康唑谷浓度比较有统计学差异(P=0.036);伏立康唑达标者与未达标者病死率比较差异无统计学意义(χ2=0.059,P=0.809)。结论 伏立康唑血药谷浓度个体差异大,因此临床有监测的必要,年龄、联用质子泵抑制剂对伏立康唑血药谷浓度影响较大,制定给药方案时需考虑这些因素的影响。
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[Abstract]
Objective To observe the changes in voriconazole plasma trough concentration in critical patients,and explore its optimal dosage. Methods A retrospective analysis was carried out in critical patients with voriconazole and voriconazole therapeutic drug monitoring (TDM) in intensive care unit (ICU) of the Affiliated Drum Tower Hospital of Nanjing University Medical School from December 2014 to December 2016.The patients' age, sex, dose, and other general information, voriconazole trough concentrations, influence of proton pump inhibitors (PPIs) on plasma trough concentrations, efficacy were analyzed retrospectively. Results 150 times of voriconazole plasma trough concentration in 99 patients were enrolled, and it was found that only 76.00% (114/150) reached the target concentration (1-5.5 mg/L), 13.33% (17/150) < 1 mg/L and 12.67% (19/150) > 20 mg/L. Significant difference was observed between old patients (≥ 60 years old) and other patients (< 60 years old) (P < 0.05), age (P=0.000) was found to be correlated to plasma trough concentrations by multiple linear regression analysis, but sex, body weight, weighted dose, APACHE2 score, total bilirubin and albumin don,t; there was no significant difference of plasma trough concentration of voriconazole between the use of PPIs, the concentration tended to increase with pantoprazole (P=0.054), and was statistically different compared with that of esomeprazole (P=0.036); There was no significant difference in mortality between patients with targeting trongh plasma concentrations and those without (χ2=0.059, P=0.809). Conclutions Voriconazole plasma trough concentration has great variation between individuals, so constant monitoring is necessary. Age and the combination of PPIs show a relatively significant influence on the serum trough concentrations,and they should be taken into consideration in dosage to be given.
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