Telmisartan pharmacokinetics in Japanese renal transplant recipients
Telmisartan pharmacokinetics in Japanese renal transplant recipients
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DOI：
10.1016/j.cca.2008.09.020
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发表时间：
2009-01-01
影响因子：
5
通讯作者：
Suzuki, Toshio
中科院分区：
文献类型：
--
作者：
Miura, Masatomo;Satoh, Shigeru;Suzuki, Toshio
背景资料：替米沙坦通过有机阴离子转运多肽（OATP/基因SLCO）进入人肝细胞，并通过尿苷二磷酸-葡萄糖醛酸基转移酶（UGT）葡萄糖醛酸化为酰基葡糖苷酸，然后通过转运蛋白（如多药耐药1（MDR 1/基因ABCB 1）、多药耐药蛋白2（MRP 2/基因ABCC 2）或乳腺癌耐药蛋白（BCRP/基因ABCG 2））排泄。我们阐明了UGT（1A 1，1A 6，1A 7，1A 9和2B 7），SLCO（1B 1，1B 3和2B 1），ABCB 1，ABCC 2和ABCG 2多态性与稳态替米沙坦药代动力学在12个日本肾移植recipients.Methods的关联：受体给予40毫克的替米沙坦至少6个月。移植后1年采集血液样本。结果：ABCC 2 - 24 C/T基因型受试者血浆中替米沙坦浓度显著高于C/C基因型受试者（分别为96.8ng/ml和57.4ng/ml，P=0.0094）。在ABCC 2 - 24 C/C基因型中，口服给药后13 h观察到替米沙坦的第二个血药浓度峰，但ABCC 2 - 24 C/T基因型组未观察到。其他转运体如SLCO 1B 3、ABCB 1和ABCG 2或UGTs基因型组间替米沙坦药代动力学无显著差异。结论：ABCC 2基因多态性对替米沙坦药代动力学的个体间变异有显著影响。MRP 2可能主要参与人体中替米沙坦的药代动力学。(C)2008 Elsevier B. V.保留所有权利。
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.