肾移植患者中伏立康唑对他克莫司药代动力学的影响
Effects of voriconazole on pharmacokinetics of tacrolimus in renal transplantation patients
张丹 1王超 2裴广辉 3张弋2
作者信息
- 1. 天津医科大学一中心临床学院,天津 300070
- 2. 天津市第一中心医院药学部,天津 300192
- 3. 天津市第一中心医院肾移植科,天津 300192
- 折叠
摘要
目的 探讨肾移植患者口服伏立康唑(VRC)对他克莫司(TAC)药代动力学的影响.方法 纳入在服用VRC前均已口服TAC超过2 d并达到稳态血药浓度的肾移植患者为研究对象,在服用VRC 200或400 mg·d-1后的第3、5和10天,用高效液相色谱方法测定TAC的药物谷浓度(C0),用聚合酶链反应法检测基因型,并比较联合使用VRC后TAC药代动力学的变化情况.结果 11例肾移植患者使用VRC后,TAC C0为3～8 μg·L-1,浓度剂量为原剂量的50.00％～87.50％.VRC对TAC的影响程度在个体间存在明显差异.在服用VRC 后的 TAC C0平均值明显高于 VRC 前[(12.14±3.89)vs(5.20±2.79)vg·L-1].11例肾移植患者根据细胞色素P450(CYP)2C19-CYP3A5基因多态性进行分组,在联合用药情况下,慢代谢组TAC在第3、5和10天的C0/剂量均显 著 高于快 代谢组[(582.10±252.30)vs(439.03±166.08),(873.71±449.22)vs(666.60±168.00),(852.10±505.73)vs(261.50±81.98)μg·L-1·mg-1·kg;均P＜0.01].结论 肾移植患者口服VRC对TAC药代动力学有着显著的影响,两者联合应用TAC剂量需要减少原始剂量1/3的原则已经不适用,可能与VRC本身的药代动力学以及CYP2C19/CYP3A5基因多态性有关,建议在联合使用VRC和TAC时定期监测TAC药物浓度.
Abstract
Objective To explore the effects of oral voriconazole(VRC)on the pharmacokinetics of tacrolimus(TAC)in renal transplant patients.Methods Renal transplant patients who had taken TAC orally for more than 2 days and achieved steady-state plasma concentration before taking VRC.The trough concentration of TAC was measured on the 3rd,5th and 10th days after VRC 200 or 400 mg·d-1 administration.The trough concentration(C0)of TAC was determined by high performance liquid chromatography.The genotypes of TAC were determined by polymerase chain reaction and the pharmacokinetics of TAC after combined use of VRC were compared.Results After the use of VRC,the TAC C0 of 11 renal transplant patients was 3-8 μg·L-1,and the concentration of TAC ranged from 50.00％to 87.50％of the original dose.Additionally,the impact of VRC on TAC varied significantly among individuals.The mean TAC C0 value after VRC administration was significantly higher than the value before VRC[(12.14±3.89)vss(5.20±2.79)μg·L-1].Eleven renal transplant patients were grouped according to cytochrome P450(CYP)2C19-CYP3A5 gene polymorphism,under the condition of combined administration,the C0/dose of TAC in the slow metabolizer group was higher than that in the fast metabolizer group on the 3rd,5th and 10th days[(582.10±252.30)vs(439.03±166.08),(873.71±449.22)vs(666.60±168.00),(852.10±505.73)vs(261.50±81.98)μg·L-1·mg-1·kg;all P＜0.01].Conclusion TAC pharmacokinetics was significantly affected by the VRC in renal transplant recipients,and the principle that TAC dose needed to be reduced by one-third of the original dose was no longer applicable,which may be related to the pharmacokinetics of the VRC itself and the gene polymorphism of CYP2C19/CYP3A5 enzyme.It is recommended to regularly monitor the concentration of TAC when VRC and TAC are used in combination.
关键词
他克莫司/伏立康唑/肾移植/药代动力学/药物相互作用Key words
tacrolimus/voriconazole/renal transplant/pharmacokinetics/drug-drug interaction引用本文复制引用
出版年
2024
国家科技期刊平台
NSTL
万方数据