五酯胶囊提高他克莫司血药浓度的耐受性研究

Tolerance to the effects of WZ capsules on the blood concentration of tacrolimus

目的:通过分析他克莫司(tacrolimus, TAC)联合五酯胶囊(WZ capsules, WZ)治疗肾病综合征患者的他克莫司血药浓度及相关临床资料,探究五酯胶囊影响他克莫司血药浓度的变化规律,为临床合理用药提供依据。方法:收集中国医科大学附属盛京医院2018年10月至2019年12月服用他克莫司进行治疗的肾病综合征患者为研究对象,记录患者的人口学信息、合并药物、药物浓度等,分析五酯胶囊对他克莫司血药浓度的影响,并以五酯胶囊合用时长将患者分为合用前、合用1~3个月、合用3~6个月3组,分析五酯胶囊对他克莫司血药浓度影响的时间变化规律。结果:共纳入72例患者,TAC组与TAC+WZ组的标准化血药浓度分别为(135.37±95.18),(308.90±183.31)ng·kg·mL^(-1)·mg^(-1),差异有统计学意义(P<0.01)。从TAC+WZ组筛选出能够完整收集到合用前至合用6个月数据的患者20例,所有患者血药浓度在合用1~2个月均显著提高,平均升高(185.3±94.5)%,18例患者在联合用药2个月后血药浓度呈不同程度的下降,平均降低(21.7±15.8)%。结论:他克莫司联合五酯胶囊给药,可显著升高他克莫司全血药物谷浓度,合并用药患者他克莫司血药浓度在联合用药2个月后出现一定程度降低,至合用后3个月趋于稳定,提示可能出现耐受性。因此他克莫司合用五酯胶囊时应关注合用2~3个月时段他克莫司血药浓度的变化,及时调整剂量,保证治疗的安全及有效性。

OBJECTIVE To analyze the blood drug concentrations of tacrolimus inpatients with nephrotic syndrome taking tacrolimus and WZ capsules and examine the effect of WZ capsules on the elevated concentration of tacrolimus so as to provide rationales for rational drug use in clinical practices.METHODS A total of 72 patients diagnosed with nephrotic syndrome and treated with tacrolimus from October 2018 to December 2019 were collected as subjects.General status, combination of medications and blood concentration of tacrolimus were recorded.The effect of WZ capsules on the blood concentration of tacrolimus was examined.Then according to the timing of combined use of WZ capsules, they were divided into three groups of pre-using, using for 1-3 months and using for 3-6 months.Finally the effects of combined WZ capsules on the blood concentration of tacrolimus over time were analyzed. RESULTS A total of 72 patients were included.The standardized blood drug concentrations of tacrolimus were(135.37±95.18)and(308.90±183.31)ng·kg·mL^(-1)·mg^(-1)in TAC and TAC+WZ groups with significant difference(P<0.01).Twenty patients in TAC+WZ group with data from pre-drug combination to 6 months’ drug combination were selected.All drug concentrations increased significantly in combination WZ capsule for 1-2 months.The average elevation was around(185.3±94.5)%.However, after 2 months of combined use, there were different degrees of decline in 18 patients.The average decline was around(21.7±15.8)%.CONCLUSION WZ capsules could significantly increase whole blood concentrations of tacrolimus.However, the blood concentration of tacrolimus decreased after 2 months and stabilized after 3 months of combined treatment.Thus it hints at a possibility of tolerance and attention should be paid to the changes of tacrolimus blood concentration at 2-3 months of combined use of WZ capsules to ensure the safety and effectiveness of treatment.