恶性血液病患者中伏立康唑血药浓度监测及其影响因素的探讨  

Monitoring voriconazole concentrations and identifying the influence factors in patients with hematological malignancy

作　　者：王陶陶[1] 胡萨萨[1] 尤海生[1] 陈思颖[1] 陈丽梅[2] 董海燕[1] 董亚琳[1] WANG Tao-tao;HU Sa-sa;YOU Hai-sheng;CHEN Si-ying;CHEN Li-mei;DONG Hai-yan;DONG Ya-lin(Department of Pharmacy;Department of Hematology, The First Affiliated Hospital of Xi＇an J iaotong University, Shaanxi Xi＇an 710061 ,China)

机构地区：[1]西安交通大学第一附属医院药学部,陕西西安710061 [2]西安交通大学第一附属医院血液内科,陕西西安710061

出　　处：《中国医院药学杂志》2018年第7期693-696,707,共5页Chinese Journal of Hospital Pharmacy

基　　金：国家自然基金项目(编号:81473177)

摘　　要：目的:探讨伏立康唑谷浓度(Cm in)在血液病患者的分布特征。方法:采用高效液相色谱(HPLC)法测定伏立康唑Cm in,采用SPSS软件分析伏立康唑Cm in和协变量之间的相关性,探讨影响伏立康唑Cm in的因素。结果:本研究中共监测了46例恶性血液病患者的66个血样,伏立康唑Cm in具有较大的个体间差异,平均浓度为(1.57±1.40)μg·m L-1,只有53.0%的Cm in在治疗窗范围内。其中,静脉滴注伏立康唑患者的Cm in显著高于口服伏立康唑患者的Cm in[(2.69±1.52)vs.(1.31±1.53)μg·m L-1,P<0.05]。伏立康唑Cm in与患者的年龄呈显著的正相关性。CYP2C19慢代谢者的伏立康唑Cm in高于快代谢者和中间代谢者,合并使用肝药酶抑制剂可增加患者的伏立康唑Cm in,而合并使用肝药酶诱导剂可降低患者的伏立康唑Cm in。研究中并没发现伏立康唑可引起患者谷草转氨酶、谷丙转氨酶、总胆红素和血肌酐值显著增加。结论:伏立康唑在恶性血液病患者中的谷浓度低,其给药途径、患者的年龄和CYP2C19基因型及患者是否合用CYP2C19抑制剂或诱导剂对伏立康唑Cm in有影响。在恶性血液病患者使用伏立康唑时,应注意监测伏立康唑Cm in,以保证伏立康唑Cm in在治疗窗范围内,从而提高伏立康唑治疗的有效性。OBJECTIVE To explore the characteristics of voriconazole trough concentrations（ Cm in） in patients with hematological malignancy. METHODS Voriconazole Cm inwas measured by high performance liquid chromatography（ HPLC）,and the SPSS software was used to explore the factors influencing voriconazole Cm inby building the relationship of voriconazole Cm inand covariates. RESULTS Totally 66 samples were collected from 46 patients. A large inter-individual variability was observed in the voriconazole Cm in,and only 53. 0 % of voriconazole Cm inwere in the range of therapeutic window. The average concentration of voriconazole Cm inwas（ 1. 57 ± 1. 40） μg·m L-1. There was a significant difference between voriconazole Cm inin oral versus intravenous treatment [（ 2. 69 ±1. 52） vs.（ 1. 31 ± 1. 53） μg·m L-1,respectively,P〈 0. 05]. Voriconazole Cm inwas significantly positively correlated with the age of patients. The voriconazole Cm inin poor metabolizers was higher than in extensive metabolizer and intermediate metabolizer. Patients also using liver enzyme inhibitors had increased voriconazole Cm in,while the liver enzyme inducer reduced the patient＇s voriconazole Cm in. In the present study,voriconazole had not increased the values of aspartate aminotransferase,alanine aminotransferase,total bilirubin or serum creatinine of patients. CONCLUSION The voriconazole Cm inin patients with hematological malignancy is low. The administration routes of voriconazole,the age and CYP2 C19 genetic polymorphism of patients,and combination with CYP2 C19 inhibitor or inducer have influence on voriconazole Cm in. In clinical practice,voriconazole Cm inshould be monitored in patients with hematological malignancy during voriconazole therapy,which can help to maintain voriconazole Cm inin the range of therapeutic window and improve the effectiveness of voriconazole therapy.

关 键 词：伏立康唑 恶性血液病患者 治疗药物监测 CYP2C19基因型 

分 类 号：R978.5[医药卫生—药品]