伏立康唑治疗儿童侵袭性真菌感染血药浓度与疗效相关性研究
投稿时间:2021-06-13  修订日期:2021-12-08  点此下载全文
引用本文:桂明珠,李静,谢晓恬,李志玲.伏立康唑治疗儿童侵袭性真菌感染血药浓度与疗效相关性研究[J].药学实践杂志,2022,40(4):359~363
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作者单位E-mail
桂明珠 上海市宝山区罗店医院, 上海 201908  
李静 上海市宝山区罗店医院, 上海 201908  
谢晓恬 上海市同济医院, 上海 200333  
李志玲 上海交通大学医学院附属儿童医院, 上海 200064 lizhiling22@163.com 
中文摘要:目的 探索伏立康唑治疗儿童侵袭性真菌感染的剂量、血药浓度与疗效的相关性。方法 收集2019年1月至2019年12月,使用伏立康唑治疗的68例儿童侵袭性深部真菌感染病例,采用高效液相色谱法检测伏立康唑的血药谷浓度,统计分析伏立康唑的不同剂量与血药浓度和临床疗效的相关性。结果 检测显示不同给药剂量的血药谷浓度分别为:<4.0 mg/kg(6例),谷浓度在0.4~3.31 μg/ml (r=0.613,P=0.195);4.0~7.0 mg/kg(44例),谷浓度在0.35~7.02 μg/ml(r=0.325,P=0.018);>7.0 mg/kg(18例),谷浓度在1.46~12.45 μg/ml (r=0.584,P<0.023),3组间差异有统计学意义(F=7.270, P=0.026)。68例患儿中总体有效58例(85.3%),无效10例(14.7%)。上述不同谷浓度的疗效分别为:<1.0 μg/ml组14例,有效10例(71.4%),无效4例;1.0~5.5 μg/ml组48例,有效44例(91.7%),无效4例;>5.5 μg/ml组6例,有效4例(66.7%),无效2例。3组间差异有统计学意义(χ=5.360, P=0.039)。10例出现不良反应(14.7%),主要为轻度肝功能损伤,不影响治疗,保肝治疗后可恢复。结论 研究显示伏立康唑治疗儿童侵袭性真菌感染总体安全有效,且存在明显的剂量-血药浓度与疗效的相关性。因此,进一步开展药动学与疗效相关研究,有利于实现理想的个体化治疗。
中文关键词:伏立康唑  侵袭性真菌感染  儿童  血药浓度  临床疗效
 
Study on the relationship between blood concentration and efficacy of voriconazole in the treatment of pediatric invasive fungal infection
Abstract:Objective To explore the correlation between dose, blood concentration and efficacy of voriconazole in the treatment of invasive fungal infection in children. Methods 68 children treated with voriconazole during January 2019 to December 2019 were collected. The plasma concentration of voriconazole was assayed by high performance liquid chromatography (HPLC). The correlation between blood concentration and clinical efficacy was statistically analyzed. Results Different drug blood concentrations were obtained with different dosages: <4.0 mg/kg (6 cases) with the trough concentration ranged from 0.4 to 3.31 μg/ml (r=0.613, P=0.195). (4.0 - 7.0) mg/kg (44 cases), ranged from 0.35 to 7.02 μg/ml (r=0.325, P=0.018); >7.0 mg/kg (18 cases), ranged from 1.46 to 12.45 μg/ml (r=0.584,P<0.023). There was a difference between the three groups (F=7.270, P=0.026). The relationship between the drug blood concentration and the therapeutic effect was obvious. In the <1.0 μg/ml group of 14 cases, 10 cases (71.4%) were effective, and 4 cases were ineffective. In the 1.0 - 5.5 μg/ml group of 48 cases, 44 cases (91.7%) were effective, and 4 cases were ineffective. In the >5.5 μg/ml group of 6 cases, 4 cases (66.7%) were effective and 2 cases ineffective. The difference among the three groups was obvious (χ2=5.360, P=0.039). Among the 68 cases, 58 cases (85.3%) were effective, and 10 cases (14.7%) were ineffective. Adverse reactions occurred in 10 cases (14.7%) with mild liver function injury, which did not affect the treatment and recovered with liver protection treatment. Conclusion This study showed that voriconazole was generally safe and effective in the treatment of invasive fungal infections in children. There was a significant dose-blood concentration and efficacy correlation. Further studies on pharmacokinetics and efficacy should be carried out to optimize the individualized treatment.
keywords:voriconazole  invasive fungal infection  children  drug concentration  clinical efficacy
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