Effects of CYP3A5 polymorphism and the tacrolimus 12 h concentration on tacrolimus-induced acute renal dysfunction in patients with lupus nephritis

被引：1

作者：

Niioka, Takenori ^{[1
]}

Komatsuda, Atsushi ^{[2
]}

Kato, Shotaro ^{[1
]}

Togashi, Masaru ^{[2
]}

Okuyama, Shin ^{[3
]}

Omokawa, Ayumi ^{[4
]}

Nara, Mizuho ^{[2
]}

Wakui, Hideki ^{[5
]}

Takahashi, Naoto ^{[2
]}

Miura, Masatomo ^{[1
]}

机构：

[1] Akita Univ Hosp, Dept Pharm, Akita, Japan

[2] Akita Univ, Grad Sch Med, Dept Hematol, Nephrol,Rheumatol, 1-1-1 Hondo, Akita 0108543, Japan

[3] Akita Univ Hosp, Ctr Kidney Dis & Transplantat, Akita, Japan

[4] Akita Univ, Grad Sch Med, Dept Gen Internal Med & Clin Lab Med, Akita 0108543, Japan

[5] Akita Univ, Grad Sch Engn & Resource Sci, Dept Life Sci, Akita 0108543, Japan

来源：

XENOBIOTICA | 2015年 / 45卷 / 12期

基金：

日本学术振兴会;

关键词：

Acute renal dysfunction; CYP3A5; polymorphism; lupus nephritis; tacrolimus; therapeutic drug monitoring; SINGLE NUCLEOTIDE POLYMORPHISMS; PRIMARY KIDNEY-TRANSPLANTATION; SOLID-ORGAN TRANSPLANTATION; JAPANESE POPULATION; OPEN-LABEL; PHARMACOKINETICS; FK506; TRIAL; PHARMACODYNAMICS; EFFICACY;

D O I：

10.3109/00498254.2015.1045571

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

1. The purpose of the present study was to investigate the effect of tacrolimus concentration in blood 12 h after administration (C-12h) on acute renal dysfunction in patients with lupus nephritis (LN) taking tacrolimus once daily. 2. Five of the 35 LN patients experienced tacrolimus-induced acute renal dysfunction. 3. The average annual C-12h of tacrolimus was higher for patients with events of elevated serum creatinine level than for patients not experiencing these events [6.4 (5.6-8.8) versus 2.8 (2.2-4.6) ng/mL, respectively, p = 0.001]. 4. The average annual tacrolimus C-12h was higher for patients with CYP3A5*3/*3 (PM) than for patients with the CYP3A5*1 allele (EM) [4.6 (3.2-6.6) versus 2.5 (2.0-3.1) ng/mL, respectively, p = 0.002]. 5. The area under the receiver operating characteristic was 0.887, which gave the best sensitivity (80.0%) and specificity (86.7%) at a tacrolimus C-12h (average annual C-12h or C-12h at events) threshold of 5.2 ng/mL. 6. C-12h measurements, CYP3A5 genotyping and dose adjustments of tacrolimus should be performed to prevent acute renal dysfunction in LN patients taking tacrolimus once daily.

引用

页码：1147 / 1153

页数：7

共 33 条

[1] Outcomes of maintenance therapy with tacrolimus versus azathioprine for active lupus nephritis: a multicenter randomized clinical trial [J].