ABCB1基因单核苷酸多态性对伏立康唑血药浓度的影响1例并文献复习  

Effect of Single Nucleotide Polymorphism of ABCB1 Gene on Plasma Concentration of Voriconazole:A Case Report and Literature Review

作　　者：林志强[1] 吴水发 吴娜梅 LIN Zhi-qiang;WU Shui-fa;WU Na-mei(Department of Pharmacy,Quanzhou First Hospital Affiliated to Fujian Medical University,Quanzhou 362000,China)

机构地区：[1]福建医科大学附属泉州第一医院药剂科,福建泉州362000

出　　处：《海峡药学》2023年第7期52-56,共5页Strait Pharmaceutical Journal

基　　金：泉州市科技计划资助,2021年泉州市人才领域科研项目(项目编号:2021C036R)。

摘　　要：目的了解腺苷三磷酸结合盒转运体B1(ABCB1)基因单核苷酸多态性对伏立康唑血药浓度的影响。方法对我院1例急性淋巴细胞性白血病合并侵袭性肺曲霉病的患者在给予伏立康唑治疗期间,ABCB1基因单核苷酸多态性对伏立康唑体内代谢的影响进行分析,并以“伏立康唑”、“腺苷三磷酸结合盒转运体B1”或“ABCB1”为主题词检索万方、维普和中国知网数据库,以“Voriconazole”、“ABCB1”为主题词检索Pubmed数据库,检索国内外报道的ABCB1(c.3435C>T,rs1045642)单核苷酸多态性影响伏立康唑体内代谢的病例,筛选并总结分析病例资料。结果本院报道的病例,当伏立康唑维持剂量为200 mg(4.26 mg·kg^(-1))静滴时,初始谷浓度为0.25μg·mL^(-1)。经多次治疗药物监测(Therapeutic drug monitoring,TDM),同时进行ABCB1及CYP2C19基因测序,将维持剂量提高到300 mg(6.38 mg·kg^(-1))静滴或350 mg(7.45 mg·kg^(-1))口服时,伏立康唑谷浓度达到目标浓度范围。在排除了药物相互作用、CYP2C19基因多态性及炎症的影响后,ABCB1(c.3435C>T,rs1045642)TT基因型可能与伏立康唑谷浓度降低有关。检索到1篇文献,报道案例177例。年龄<12岁的患者有31人,ABCB1(c.3435C>T,rs1045642)TT基因型有5人(16.13%),伏立康唑中位给药剂量为8.33 mg·kg^(-1),高于CC、CT基因型,但无显著性差异;年龄>12岁的患者有146人,ABCB1(c.3435C>T,rs1045642)TT基因型有19人(13.02%),伏立康唑谷浓度中位数为1.293μg·mL^(-1),低于CC、CT基因型,但无显著性差异。结论ABCB1(c.3435C>T,rs1045642)TT基因型可能与伏立康唑谷浓度降低有关,但需要进行更多的研究来验证。伏立康唑药代动力学受多种因素的影响,遗传多态性仅是其中之一,基因分型不能替代TDM,但可作为TDM的补充,在伏立康唑不能达到目标治疗浓度时,作为剂量或药物调整的辅助决策工具。OBJECTIVE To investigate the effect of single nucleotide polymorphism of ATP-binding cassette subfamily B member 1(ABCB1)gene on voriconazole plasma concentration.METHODS The effect of ABCB1 gene single nucleotide polymorphism on voriconazole metabolism in a patient with acute lymphocytic leukemia complicated with invasive pulmonary aspergillosis was analyzed.Wanfang,VIP,CNKI and Pubmed databases were searched with“voriconazole”and“ABCB1”as the key words.The cases reported at home and abroad that ABCB1(c.3435C>T,rs1045642)single nucleotide polymorphism affected voriconazole metabolism in vivo were retrieved,screen and summarize the case data.RESULTS In the case reported in our hospital,when the maintenance dose of voriconazole was 200 mg(4.26 mg·kg^(-1))intravenously,the initial trough concentration was 0.25μg·mL^(-1).After multiple therapeutic drug monitoring(TDM)and simultaneous ABCB1 and CYP2C19 gene sequencing,the maintenance dose was increased to 300 mg(6.38 mg·kg^(-1))intravenously or 350 mg(7.45 mg·kg^(-1))orally,the trough concentration of voriconazole reach the target concentration range.ABCB1(c.3435C>T,rs1045642)TT genotype may be related to the decrease of voriconazole trough concentrations after excluding the effects of drug interaction,CYP2C19 gene polymorphism and inflammation.One document was retrieved and 177 cases were reported.There were 31 patients with age<12 years old,and 5 patients with ABCB1(c.3435C>T,rs1045642)TT genotype(16.13%).The median dose of voriconazole was 8.33 mg·kg^(-1),which was higher than that of CC and CT genotypes,but there was no significant difference.There were 146 patients aged>12 years,19 patients with ABCB1(c.3435C>T,rs1045642)TT genotype(13.02%),and the median trough concentration of voriconazole was 1.293μg·mL^(-1),lower than CC and CT genotypes,but there was no significant difference.CONCLUSION The ABCB1(c.3435C>T,rs1045642)TT genotype may be related to the decrease of voriconazole trough concentration,but more studies are needed to verify it.The ph

关 键 词：伏立康唑 腺苷三磷酸结合盒转运体B1 基因 单核苷酸多态性 治疗药物监测 

分 类 号：R969.1[医药卫生—药理学]