Influence of CYP3A5, ABCB1 and NR1I2 polymorphisms on prednisolone pharmacokinetics in renal transplant recipients

被引：43

作者：

Miura, Masatomo ^{[1
]}

Satoh, Shigeru ^{[2
]}

Inoue, Kazuyuki ^{[1
]}

Kagayaa, Hideaki ^{[1
]}

Saito, Mitsuru ^{[2
]}

Inoue, Takamitsu ^{[2
]}

Habuchi, Tomonori ^{[2
]}

Suzuki, Toshio ^{[1
]}

机构：

[1] Akita Univ Hosp, Dept Pharm, Akita 0108543, Japan

[2] Akita Univ, Sch Med, Dept Urol, Akita 010, Japan

来源：

STEROIDS | 2008年 / 73卷 / 11期

基金：

日本学术振兴会;

关键词：

prednisolone; tacrolimus; CYP3A5; P-glycoprotein; pregnane X receptor;

D O I：

10.1016/j.steroids.2008.04.002

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

The objective of this study was to evaluate whether genetic polymorphisms of CYP3A5 (A6986G, CYP3A5*3), ABCB1 (C1236T, G2677T/A, C3435T) and NR1I2 (A7635G) significantly impact the pharmacokinetics of prednisolone in renal transplant recipients. Ninety-five recipients were given repeated doses of triple therapy immunosuppression consisting of prednisolone, tacrolimus and mycophenolate mofetil. Twenty-eight days after renal transplantation, plasma prednisolone concentrations were measured by high-performance liquid chromatography. Comparisons of the CYP3A5 and ABCB1 genotypes revealed no significant differences in the prednisolone pharmacokinetics. The mean prednisolone C-max for recipients (n = 14) having both the ABCB1 3435CC genotype and the CYP3A5*3/*3 genotype was significantly higher than those (n = 11) having both ABCB1 3435TT and CYP3A5*3/*3 genotypes (180 ng/mL versus 129 ng/mL, P = 0.0392). The plasma concentrations of prednisolone in recipients having both ABCB1 3435CC and CYP3A5*3/*3 genotypes tended to be higher than those having both ABCB1 3435TT and CYP3A5*3/*3 genotypes. The mean AUC(0-24) and C.. values for prednisolone in recipients having the NR1I2 7635G allele (AG: n = 45, GG: n = 32) were significantly lower than in patients having the 7635AA allele (n = 18) (7635GG versus 7635AA, P = 0.0308 for AUC(0-24), P = 0.0382 for C-max of prednisolone). In conclusion, NR1I2 (A7635G) rather than CYP3A5 or ABCB1 allelic variants affected patient variability of plasma prednisolone concentration. Recipients carrying the NR1I2 7635G allele seemed to possess higher metabolic activity for prednisolone in the intestine, greatly reducing its maximal plasma concentration. (c) 2008 Elsevier Inc. All rights reserved.

引用

页码：1052 / 1059

页数：8

共 31 条

[1] Pharmacokinetic interaction between corticosteroids and tacrolimus after renal transplantation [J].