基于血药浓度监测和CYP2C19基因检测的伏立康唑疗效及药物不良反应相关性临床研究  

Based on blood drug concentration monitoring and CYP2C19 genotype detection of voriconazole efficacy and adverse drug reaction correlation clinical study

作　　者：陈金成[1] 许秋霞[1] 庄奕筠[1] 张吟[1] 陈彩云[1] CHEN Jin-cheng;XU Qiu-xia;ZHUANG Yi-jun;ZHANG Yin;CHEN Cai-yun(Department of Pharmacy,The Second Affiliated Hospital of Fujian Medical University,Quanzhou 362000,Fujian Province,China)

机构地区：[1]福建医科大学附属第二医院药学部,福建泉州362000

出　　处：《中国临床药理学杂志》2023年第13期1827-1830,共4页The Chinese Journal of Clinical Pharmacology

基　　金：福建省科技厅课题基金资助项目(2020J01213)。

摘　　要：目的 探索伏立康唑血药浓度监测和细胞色素P450 2C19(CYP2C19)基因型检测疗效及药物不良反应相关性。方法 收集使用伏立康唑治疗并同时进行血药浓度监测及CYP2C19基因型检测的病例,用高效液相色谱法及微量荧光法检测伏立康唑的血药谷浓度及CYP2C19基因型,按照血药浓度分为低谷浓度组(<1.0μg·mL^(-1))、中谷浓度组(1.0~5.5μg·mL^(-1))和高谷浓度组(>5.5μg·mL^(-1)),按照基因型分为快代谢型组、中间代谢型组和慢代谢型组,统计分析伏立康唑血药浓度及CYP2C19基因型临床疗效、药物不良反应的相关性。结果 本研究总体有效率和药物不良反应发生率分别为79.59%和19.38%。低谷浓度组21例(21.43%)、中谷浓度组66例(67.35%)、高谷浓度组11例(11.22%);快代谢型组33例(33.67%),中间代谢型组54例(55.10%),慢代谢型组11例(11.22%)。低谷、中谷和高谷浓度组的治疗有效率分别为52.38%、80.30%和72.72%,药物不良反应发生率分别为9.52%、18.18%和45.45%,血药浓度低谷浓度组治疗有效率与中谷浓度组、高谷浓度组比较,差异有统计学意义(P<0.05),低谷、中谷和高谷浓度组药物不良反应发生率比较,差异有统计学意义(P<0.05)。快、中间和慢代谢型组有效率分别为78.79%、79.63%和72.73%;药物不良反应发生率分别为15.15%、18.52%和18.18%,3组间比较,上述指标差异均无统计学意义(均P>0.05);而快、中间和慢代谢型组谷浓度平均值分别为1.82、2.83和3.70μg·mL^(-1),快、中间和慢代谢型组谷浓度比较,差异有统计学意义(P<0.05)。结论 研究表明对伏立康唑进行血药浓度监测有利于患者更好的进行个体化治疗,而基因检测对患者的影响可能仅体现在血药浓度的差异上,需要进一步开展伏立康唑药代动力学与疗效相关研究。Objective To explore the correlation between voriconazole concentration monitoring and cytochrome P450 2C19(CYP2C19)genotype detection of efficacy and adverse drug reactions.Methods Patients treated with voriconazole were collected for serum concentration monitoring and CYP2C19 genotype detection.Serum trough concentration and CYP2C19 genotype of voriconazole were detected by HPLC and micro-fluorescence method.Patients were divided into low trough concentration group(LCG,<1.0 μg·mL^(-1)),medium trough concentration group(MCG,1.0-5.5 μg·mL^(-1)) and high trough concentration group(HCG,>5.5 μg·mL^(-1)).Patients were divided into extensive metabolizer(EM) group,intermediate metabolizer(IM)group and poor metabolizer(PM) group according to genotype.The correlation between voriconazole concentration and CYP2C19 genotype and clinical efficacy and adverse drug reactions was analyzed statistically.Results The overall effective rate and incidence of adverse drug reactions were 79.59% and 19.38%,respectively.There were 21 cases(21.43%) of the LCG,66 cases(67.35%) of the MCG,and 11 cases(11.22%) of the HCG.There were 33 cases(33.67%) in the EM group,54 cases(55.10%) in the IM group,and 11 cases(11.22%) in the PM group.The effective rate of LCG,MCGand HCGwere 52.38%,80.30% and 72.72%,and the incidence of adverse drug reactions were 9.52%,18.18% and 45.45%,respectively.The effective rate of LCGwas compared with that of MCG and HCG.The difference was statistically significant(P<0.05),there was no significant difference between the MCG group(P<0.05),there was statistically significant difference in the incidence of adverse drug reactions in blood drug concentration among 3 groups(P<0.05),indicating that blood concentration monitoring is helpful to improve the effective rate of clinical treatment,and high trough concentration is more likely to produce adverse drug reactions.The effective rates of EM,IM and PM groups were 78.79%,79.63% and 72.73%,respectively.The incidence of adverse drug reactions were 15.15%,18.52% and 18.

关 键 词：伏立康唑 血药浓度 基因检测 临床疗效 药物不良反应 

分 类 号：R97[医药卫生—药品]