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

Muraki,Yuichi; Mizuno,Shugo; Nakatani,Kaname; Wakabayashi,Hiroki; Ishikawa,Eiji; Araki,Toshimitsu; Taniguchi,Akira; Isaji,Shuji; Okuda,Masahiro

doi:10.3892/etm.2017.5364

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

Authors:
- Yuichi Muraki
- Shugo Mizuno
- Kaname Nakatani
- Hiroki Wakabayashi
- Eiji Ishikawa
- Toshimitsu Araki
- Akira Taniguchi
- Shuji Isaji
- Masahiro Okuda
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Affiliations: Department of Pharmacy, Mie University Hospital, Tsu, Mie 514‑8507, Japan, Department of Transplantation and Hepatobiliary Pancreatic Surgery, Mie University Graduate School of Medicine, Tsu, Mie 514‑8507, Japan, Department of Molecular and Laboratory Medicine, Mie University Graduate School of Medicine, Tsu, Mie 514‑8507, Japan, Department of Orthopaedic Surgery, Mie University Graduate School of Medicine, Tsu, Mie 514‑8507, Japan, Department of Cardiology and Nephrology, Mie University Graduate School of Medicine, Tsu, Mie 514‑8507, Japan, Department of Gastrointestinal and Pediatric Surgery, Mie University Graduate School of Medicine, Tsu, Mie 514‑8507, Japan, Department of Neurology, Mie University Graduate School of Medicine, Tsu, Mie 514‑8507, Japan
Published online on: October 24, 2017 https://doi.org/10.3892/etm.2017.5364
Pages: 532-538

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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.

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