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  • Clin Transl Sci.に論文が掲載されました。（末期腎不全患者における血清タクロリムス濃度とCYP3A5多型及び血清副甲状腺ホルモンとの関係：大分大学病院薬剤部との共同研究）

新着情報

Clin Transl Sci.に論文が掲載されました。（末期腎不全患者における血清タクロリムス濃度とCYP3A5多型及び血清副甲状腺ホルモンとの関係：大分大学病院薬剤部との共同研究）

2021/06/01

Clin Transl Sci.に論文が掲載されました。（末期腎不全患者における血清タクロリムス濃度とCYP3A5多型及び血清副甲状腺ホルモンとの関係：大分大学病院薬剤部との共同研究）

Association of CYP3A5 polymorphisms and parathyroid hormone with blood level of tacrolimus in patients with end-stage renal disease

Ryota Tanaka 1, Yosuke Suzuki 2, Hiroshi Watanabe 3, Takashi Fujioka 4, Kenshiro Hirata 5, Toshitaka Shin 6, Tadasuke Ando 6, Hiroyuki Ono 1, Ryosuke Tatsuta 1, Hiromitsu Mimata 6, Toru Maruyama 3, Hiroki Itoh 1
Affiliations

Affiliations

  • 1Department of Clinical Pharmacy, Oita University Hospital, Oita, Japan.
  • 2Department of Medication Use Analysis and Clinical Research, Meiji Pharmaceutical University, Tokyo, Japan.
  • 3Department of Biopharmaceutics, Graduate School of Pharmaceutical Sciences, Kumamoto University, Kumamoto, Japan.
  • 4Laboratory of Medical Pharmaceutics, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Toyama, Japan.
  • 5Department of Clinical Pharmaceutics, Faculty of Pharmaceutical Sciences, Sojo University, Kumamoto, Japan.
  • 6Department of Urology, Faculty of Medicine, Oita University, Oita, Japan.

Abstract

Because tacrolimus is predominantly metabolized by CYP3A, the blood concentration/dose (C/D) ratio is affected by CYP3A5 polymorphism. Parathyroid hormone (PTH) expression increases in secondary hyperparathyroidism, which is frequently associated with end-stage renal disease. Recently, PTH has been shown to downregulate CYP3A expression at mRNA level. In this study, we examined the influence of CYP3A5 polymorphism on and association of serum intact-PTH (iPTH) level with blood tacrolimus concentration in patients with end-stage renal disease just before kidney transplantation. Forty-eight patients who satisfied the selection criteria were analyzed. Subjects were classified into two phenotype subgroups: CYP3A5 expressor (CYP3A5*1/*1 and *1/*3; n = 15) and CYP3A5 nonexpressor (CYP3A5*3/*3; n = 33). The blood tacrolimus C/D (per body weight) ratio was significantly lower in CYP3A5 expressors than that in CYP3A5 nonexpressors. A significant positive correlation was found between tacrolimus C/D and iPTH concentrations (r = 0.305, p = 0.035), and the correlation coefficient was higher after excluding 20 patients co-administered CYP3A inhibitor or inducer (r = 0.428, p = 0.023). A multiple logistic regression analysis by stepwise selection identified CYP3A5 polymorphism and serum iPTH level as significant factors associated with tacrolimus C/D. These results may suggest the importance of dose design considering not only the CYP3A5 phenotype but also serum iPTH level when using tacrolimus in patients who undergo renal transplantation.