伏立康唑的治疗药物监测在结核病患者中的应用  

The application of therapeutic drug monitoring of voriconazole in tuberculosis patients

作　　者：西娜 赵冠人[1] 陈明[1] 张策 王如瑾 Xi Na;Zhao Guan-ren;Chen Ming;Zhang Ce;Wang Ru-jin(Department of Pharmacy,the 8th Medical Center of Chinese PLA General Hospital,Beijing 100091;College of Pharmacy,Kunming 651700)

机构地区：[1]解放军总医院第八医学中心药剂科,北京100091 [2]昆明医科大学药学院,昆明651700

出　　处：《中国抗生素杂志》2021年第5期481-486,共6页Chinese Journal of Antibiotics

基　　金：解放军总医院第八医学中心面上课题(No.2017MS-012);北京药学会2019年临床药学研究项目。

摘　　要：目的探寻伏立康唑的血药浓度监测对同时联用利福霉素类药物与伏立康唑的结核病患者的意义。方法对伏立康唑联用及从未联用利福霉素类药物的患者,进行伏立康唑血药浓度测定,探寻利福霉素类药物对伏立康唑谷浓度的影响强度。分析不同分组条件下伏立康唑血药浓度及达标率的差异,评估血药浓度与不良反应及疗效的相关性。结果49例患者中联用利福霉素类18例,未联用31例,平均谷浓度为(2.30±1.86)mg/L。以1.0~5.5mg/L为达标范围,30例患者达标,其中联用利福霉素类药物4例,未联用26例。联用患者的平均谷浓度为(1.39±2.00)mg/L,未联用患者的平均谷浓度为(2.82±1.54)mg/L,两组间有显著性差异(P=0.008),联用患者伏立康唑的血药浓度达标率(22.22%)较未联用患者(83.87%)明显降低(P<0.001)。联用利福平与联用利福喷丁,总体达标率无显著性差异(P>0.05),但平均谷浓度利福平组显著高于利福喷丁组(P=0.024)。6例(12.24%)患者出现了不良反应,均未联用利福霉素类药物,平均谷浓度为(5.96±0.66)mg/L;治疗总有效率为69.4%,未联用患者90.3%,联用患者33.3%,两组间差异显著(P<0.001)。结论利福霉素类药物会严重降低伏立康唑血药浓度,不同利福霉素之间对伏立康唑血药浓度影响的差异不显著。对于应用利福霉素类药物的结核病患者,合用伏立康唑时应监测伏立康唑的血药浓度,据此调整剂量,以提高浓度达标率,使治疗安全有效。在浓度达标的前提下,利福霉素类药物对伏立康唑的影响不会影响其临床疗效,临床上需密切监护谷浓度>5mg/L患者不良反应的发生。Objective To explore the necessarity of therapeutic drug monitoring of voriconazole in tuberculosis patients when they use both rifamycin and voriconazole.Methods We determined the blood concentrations of voriconazole in patients using voriconazole combined with rifamycin or not,to explore the effect of rifamycin on the concentration of voriconazole.Then we analyzed the differences of voriconazole plasma concentrations and compliance rates between different groups,and evaluated the correlation between blood drug concentrations and adverse reactions and curative effects.Results In the 49 patients,18 were treated with rifamycin and voriconazole,31 only with voriconazole,and the mean concentration was(2.30±1.86)mg/L.With 1.0 to 5.5mg/L as the standard range,30 patients met the standard,including four cases with rifamycin and 26 cases without combination.The mean trough concentration of the patients with combined drugs was(1.39±2.00)mg/L,and the average trough concentration of the patients without combined drugs was(2.82±1.54)mg/L.There was significant difference between the two groups(P=0.008).The blood drug concentration compliance rate of the patients using voriconazole combined with rifamycin(22.22%)was significantly lower than that of the patients without combined drugs(83.87%)(P<0.001).There was no significant difference in the overall compliance rates between rifampicin and rifapentine(P>0.05),but the average concentration in the rifampicin group was significantly higher than that in the rifapentine group(P=0.024).Six patients(12.24%)whose average concentration was(5.96±0.66)mg/L had adverse reactions.The total effective rate was 69.4%,and 90.3%in the group only with voriconazole,33.3%in the other group.The difference between them was significant(P<0.001).Conclusion The rifamycin drugs can severely reduce the blood concentration of voriconazole.There is no significant difference between rifamycin drugs on their effects on the concentration of voriconazole.For TB patients with rifamycin,the therapeutic drug

关 键 词：伏立康唑 治疗药物监测 结核 利福霉素类 

分 类 号：R978.1[医药卫生—药品]