自身免疫疾病患者他克莫司稳态血药浓度影响因素的研究

Study on the factors affecting the steady-state blood concentration of tacrolimus in patients with autoimmune diseases

目的:探讨年龄、性别、用药时长和合并用药对自身免疫疾病患者他克莫司稳态血药浓度的影响,并结合肝肾功能,初步建立他克莫司稳态血药浓度参考范围,为临床个体化用药提供理论依据。方法:纳入2017年8月至2021年6月107例我院风湿免疫科应用他克莫司治疗自身免疫疾病的患者,采用SPSS 22.0统计学软件对其性别、年龄、给药剂量、合并用药、用药时长及血药浓度,肝肾功能进行分析。结果:他克莫司治疗自身免疫疾病,不同性别间血药浓度差异有统计学意义(P<0.05),不同年龄段血药浓度差异无统计学意义(P>0.05),但服药剂量差异有统计学意义(P<0.05),患者用药时长不会影响有效剂量、目标血药浓度、肝肾功能。他克莫司剂量与血药浓度呈弱相关性(r=0.115,P=0.047),血药浓度范围在4.20~9.48 ng/mL时,患者谷草转氨酶(AST)、谷丙转氨酶(ALT)、尿素水平显著增高;血药浓度范围0.08~4.20 ng/mL时,患者血清肌酐、AST、ALT、白蛋白、总胆红素(TBIL)、直接胆红素(DBIL)、间接胆红素(IBIL)等关键临床指标差异无统计学意义。结论:他克莫司用于治疗自身免疫疾病,血药浓度个体间差异度大,建议临床医生将血药浓度控制在0.08~4.20 ng/mL,并结合患者性别、年龄、临床疗效,调整剂量、优化用药方案,避免肝、肾功能潜在损害风险。

AIM:To investigate the effects of age,gender,duration of medication and combined medication on the steady-state blood concentration of tacrolimus in patients with autoimmune diseases,and to establish the reference range of steady-state blood concentration of tacrolimus in combination with liver and kidney function,so as to provide theoretical basis for clinical individual medication.METHODS:A total of 107 patients with autoimmune diseases treated with tacrolimus in the department of rheumatology and immunology of our hospital from August 2017 to June 2021 were included.Their gender,age,dose,drug combination,blood concentration,and liver and kidney function were statistically analyzed by SPSS 22.0 statistical software.RESULTS:In the treatment of autoimmune diseases with tacrolimus,there was statistical significance in the blood concentration of different genders(P0.05) and a statistically significant difference in the dosage of tacrolimus(P<0.05),the duration of medication did not affect the effective dose,target blood concentration,liver and kidney functions.There was a weak correlation between tacrolimus dose and blood concentration(r=0.115,P=0.047).When the blood concentration of tacrolimus ranged from 4.20 to 9.48 ng/mL,the levels of aspartate aminotransferase(AST),alanine aminotransferase(ALT) and urea increased significantly.When tacrolimus blood concentration ranged from 0.08 to 4.20 ng/mL,there was no significant difference in serum creatinine,AST,ALT,albumin,total bilirubin(TBIL),direct bilirubin(DBIL),indirect bilirubin(IBIL).CONCLUSION:Tacrolimus is used for the treatment of autoimmune diseases,and the blood concentration varies greatly among individuals.To avoid the risk of potential damage to liver and kidney function.It is recommended that clinicians control the blood concentration at 0.08-4.20 ng/mL,and adjust the dose and optimize the dose according to the patient’s gender,age,and clinical efficacy.