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Monitoring of peripheral blood cluster of differentiation 4+ adenosine triphosphate activity and CYP3A5 genotype to determine the pharmacokinetics clinical effects and complications of tacrolimus in patients with autoimmune diseases

机译:监测外周血中分化的4+三磷酸腺苷活性和CYP3A5基因型以确定他克莫司在自身免疫性疾病中的药代动力学临床疗效和并发症

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摘要

A total of 25 patients with autoimmune diseases receiving tacrolimus were screened using a peripheral blood cluster of differentiation 4+ adenosine triphosphate (ATP) activity assay (IMK assay) between October 2013 and July 2014. The autoimmune diseases of patients were as follows: Rheumatoid arthritis (n=15), lupus nephritis (n=6), ulcerative colitis (n=2) and myasthenia gravis (n=2). Patients were divided into two groups based on CYP3A5 genotype [expression of *1 allele: Expressor (EX; n=6) and non-expressor (NEX; n=19)]. The tacrolimus concentration and concentration/dose ratio was significantly lower in the EX group compared with the NEX group (P=0.0108 and 0.0056, respectively). In addition, all enrolled patients that presented with adverse effects belonged to the NEX group. No significant associations were observed between IMK ATP levels and the concentration or dose of tacrolimus (P=0.1092 and 0.6999, respectively). However, the IMK ATP high-level group exhibited a significantly higher occurrence rate of insufficient effect when compared with the normal and low-level groups (P=0.0014). In conclusion, the clearance of tacrolimus in patients with autoimmune diseases was affected by the CYP3A5 genotype, as previously reported in organ transplant patients. The IMK ATP level may indicate the clinical response irrespective of tacrolimus concentration.
机译:在2013年10月至2014年7月之间,使用分化型4 + 三磷酸腺苷(ATP)活性测定(IMK测定)外周血簇筛选了25例接受他克莫司治疗的自身免疫性疾病患者。患者如下:类风湿关节炎(n = 15),狼疮性肾炎(n = 6),溃疡性结肠炎(n = 2)和重症肌无力(n = 2)。根据CYP3A5基因型将患者分为两组[* 1等位基因的表达:表达子(EX; n = 6)和非表达子(NEX; n = 19)]。 EX组的他克莫司浓度和浓度/剂量比明显低于NEX组(分别为P = 0.0108和0.0056)。此外,所有出现不良反应的入组患者均属于NEX组。在IMK ATP水平和他克莫司的浓度或剂量之间未观察到显着关联(分别为P = 0.1092和0.6999)。但是,与正常组和低水平组相比,IMK ATP高水平组的不良反应发生率明显更高(P = 0.0014)。总之,如先前在器官移植患者中报道的那样,CYP3A5基因型影响了自身免疫性疾病患者中他克莫司的清除率。无论他克莫司浓度如何,IMK ATP含量均可指示临床反应。

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