Polymorphism of ORM1 is associated with the pharmacokinetics of telmisartan.
Polymorphism of ORM1 is associated with the pharmacokinetics of telmisartan.
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ORM1 多态性与替米沙坦的药代动力学相关
DOI：
10.1371/journal.pone.0070341
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Zhang W
中科院分区：
文献类型：
--
作者：
Chen WQ;Shu Y;Li Q;Xu LY;Roederer MW;Fan L;Wu LX;He FZ;Luo JQ;Tan ZR;He YJ;Zhou HH;Chen X;Zhang W
替米沙坦的药代动力学（PKs）和药效学（pd）在个体之间存在差异，主要原因尚不清楚。本研究的目的是评估ORM1以及ABCC2、ABCB1、ABCG2和SLCO1B3多态性对48名健康中国男性服用40mg替米沙坦后药物处置和血压变化的影响。方法选取48例健康男性进行试验。每个志愿者单剂量摄入40 mg替米沙坦和血浆药物浓度和测量血压(BP) 48 h。结果在这项研究中,血浆浓度时间曲线下的面积(AUC)的杂合子ORM1 113 ag)高于野生型比如,AUC (0-48) (113 aa vs 113 ag)、h·1549 .18±859.84 ng / ml vs 2313 54·h±1257 .71 ng / ml, P = 0.033), AUC(0 -∞)(113 aa vs 113 ag), 1753 .13±1060 .60 ng·h /毫升和2686 .90±1401 .87点ng·h /毫升,P = 0.016)，服用替米沙坦后5 h ORM1 113AG和113AA基因型患者舒张压（DBP）较基线BP值的变化（%）也有显著差异（P = 0.026）。本研究还发现，ABCC2 C3972T等位基因会显著影响替姆西坦的处置和服药后DBP的变化。然而，在我们的试验中，ABCG2 C421、ABCB1 C3435T和SLCO1B3 T334G的常见snp对替米沙坦的PKs或BP变化（%）没有影响。结论ORM1 A113G多态性与替姆西坦用药后PKs变异及ABCC2 C3972T相关。与野生型相比，ORM1 113AG杂合子的AUC更大，BP较基线变化（%）显著。中国临床试验注册中心ChiCTR-TNC-10000898
Background The pharmacokinetics (PKs) and pharmacodynamics (PDs) of telmisartan varies among the individuals, and the main causes remain unknown. The aim of this study was to evaluate the impact of ORM1, as well as ABCC2, ABCB1, ABCG2 and SLCO1B3 polymorphisms, on the disposition of the drug and BP change after taking 40 mg telmisartan in 48 healthy Chinese males. Method A total of 48 healthy males were included in this trial. Every volunteer ingested a single dose of 40 mg telmisartan, and the plasma drug concentration and blood pressure (BP) were measured up to 48 h. Result In this study, the area under the plasma concentration-time curve (AUC) in the heterozygotes of ORM1 113AG was higher than that in the wild-type homozygotes, AUC(0–48) (113AA vs. 113AG, 1,549.18±859.84 ng·h/ml vs. 2,313.54±1,257.71 ng·h/ml, P = 0.033), AUC(0–∞) (113AA vs. 113AG, 1,753.13±1,060.60 ng·h/ml vs. 2,686.90±1,401.87 ng·h/ml, P = 0.016), and the change(%) of the diastolic blood pressure (DBP) from the baseline BP value also showed a significant difference between the ORM1 113AG and 113AA genotypes at 5 h after taking telmisartan (P = 0.026). This study also showed that the allele of ABCC2 C3972T would affected the disposition of telmsiartan and the DBP change significantly after taking the drug. However, the common SNPs of ABCG2 C421, ABCB1 C3435T, and SLCO1B3 T334G showed no impacts on the PKs of telmisartan or BP change(%) in our trial. Conclusion The ORM1 A113G polymorphism was associated with the PKs variability after taking telmsiartan, as well as ABCC2 C3972T. The heterozygotes of ORM1 113AG showed a larger AUC and a notable BP change(%) from the baseline compared with the wild-type. Trial Registration Chinese Clinical Trial Registry ChiCTR-TNC-10000898
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影响因子：
2.6
作者：
Schwarz UI;Meyer zu Schwabedissen HE;Tirona RG;Suzuki A;Leake BF;Mokrab Y;Mizuguchi K;Ho RH;Kim RB
通讯作者：
Kim RB
影响因子：
1.6
作者：
Stangier, J;Su, CAPF;Roth, W
通讯作者：
Roth, W
影响因子：
3.9
作者：
Deo, Anand K.;Prasad, Bhagwat;Unadkat, Jashvant D.
通讯作者：
Unadkat, Jashvant D.
影响因子：
2
作者：
Moriya, Y;Nakamura, T;Okumura, K
通讯作者：
Okumura, K
DOI：
10.1007/bf01874139
发表时间：
1993-09-01
期刊：
JAPANESE JOURNAL OF HUMAN GENETICS
影响因子：
--
作者：
MASTANA, SS;JAYASEKARA, R;PAPIHA, SS
通讯作者：
PAPIHA, SS