Telmisartan pharmacokinetics in Japanese renal transplant recipients

被引:26
作者
Miura, Masatomo [1 ]
Satoh, Shigeru [2 ]
Inoue, Kazuyuki [1 ]
Saito, Mitsuru [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, Japan
基金
日本学术振兴会;
关键词
Telmisartan; UCT; OATP; MRP2; Pharmacokinetics; RESISTANCE-ASSOCIATED PROTEIN-2; HEPATIC EFFLUX TRANSPORTERS; OATP-B SLC21A9; GENETIC POLYMORPHISMS; MYCOPHENOLIC-ACID; UDP-GLUCURONOSYLTRANSFERASES; EXPRESSION; IDENTIFICATION; POPULATION; METABOLISM;
D O I
10.1016/j.cca.2008.09.020
中图分类号
R446 [实验室诊断]; R-33 [实验医学、医学实验];
学科分类号
1001 ;
摘要
Background: Telmisartan is taken up into human hepatocytes by organic anion-transporting polypeptide (OATP/ gene SLCO) and is glucuronized by uridine diphosphate-glucuronosyltransferases (UGTs) into the acylglucuronide, and it is then excreted by transporters such as multidrug resistance 1 (MDR1/gene ABCB1), multidrug resistance protein 2 (MRP2/gene ABCC2), or breast cancer resistance protein (BCRP/gene ABCG2). We elucidated the association of UGTs (1A1, 1A6, 1A7, 1A9 and 2B7), SLCOs (1B1, 1B3 and 2B1), ABCB1, ABCC2 and ABCG2 polymorphisms with steady-state telmisartan pharmacokinetics in 12 Japanese renal transplant recipients. Methods: Recipients were given 40 mg of telmisartan for at least 6 months. Blood was sampled 1 y after transplantation. Plasma concentrations of telmisartan were measured by HPLC. Results: In subjects with the ABCC2 -24C/T genotype, the maximum plasma concentration of telmisartan was significantly greater than that in C/C genotype (96.8 vs.57.4 ng/ml, respectively, P=0.0094). In ABCC2-24C/C, the second peak plasma concentration of telmisartan was observed 13 h after oral administration, but not ABCC2 -24C/T genotype group. There was no significant difference in the telmisartan pharmacokinetics between genotype groups of other transporters such as SLCO1B3, ABCB1 and ABCG2 or UGTs. Conclusions: ABCC2 genetic polymorphisms appear to strongly influence inter-individual variation of telmisartan pharmacokinetics. MRP2 may be predominantly involved in the telmisartan pharmacokinetics in humans. (C) 2008 Elsevier B.V. All rights reserved.
引用
收藏
页码:83 / 87
页数:5
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