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

监测外周血分化簇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患者中的药代动力学、临床效果和并发症

阅读:6
作者:Yuichi Muraki, Shugo Mizuno, Kaname Nakatani, Hiroki Wakabayashi, Eiji Ishikawa, Toshimitsu Araki, Akira Taniguchi, Shuji Isaji, Masahiro Okuda

Abstract

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.

特别声明

1、本页面内容包含部分的内容是基于公开信息的合理引用;引用内容仅为补充信息,不代表本站立场。

2、若认为本页面引用内容涉及侵权,请及时与本站联系,我们将第一时间处理。

3、其他媒体/个人如需使用本页面原创内容,需注明“来源:[生知库]”并获得授权;使用引用内容的,需自行联系原作者获得许可。

4、投稿及合作请联系:info@biocloudy.com。