Capability of utilizing CYP3A5 polymorphisms to predict therapeutic dosage of tacrolimus at early stage post-renal transplantation.
Capability of utilizing CYP3A5 polymorphisms to predict therapeutic dosage of tacrolimus at early stage post-renal transplantation.
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DOI：
10.3390/ijms16011840
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发表时间：
2015-01-14
影响因子：
5.6
通讯作者：
Miura M
中科院分区：
文献类型：
--
作者：
Niioka T;Kagaya H;Saito M;Inoue T;Numakura K;Habuchi T;Satoh S;Miura M
虽然CYP 3A 5多态性被用于预测他克莫司治疗的初始剂量，但遗传信息对肾移植后早期给药的预测能力尚不清楚。我们研究了多态性随时间的影响。50例日本肾移植患者接受初始口服剂量的他克莫司缓释制剂（0.20 mg/kg），每日一次，每24 h给药一次。每周对他克莫司剂量进行逐步多元线性回归分析，以确定患者临床特征的影响。在第二次移植前他克莫司给药前，CYP 3A 5 *3/*3等位基因患者的剂量调整谷浓度比CYP 3A 5 *1等位基因患者高约70%（0.97（0.78-1.17）vs. 0.59（0.45-0.87）ng/mL/mg; p < 0.001）。从移植后第14天至第28天，遗传因素（CYP 3A 5 *1或 *3）对他克莫司给药的贡献显示变异增加：第14、21和28天分别为7.2%、18.4%和19.5%。尽管他克莫司剂量仅根据术后前三天患者体重确定，但在移植后第14天，CYP 3A 5多态性对他克莫司维持剂量的影响变得明显。他克莫司从首次给药开始的剂量应使用CYP 3A 5基因型信息进行个体化。
While CYP3A5 polymorphisms are used to predict the initial dosage of tacrolimus therapy, the predictive capability of genetic information for dosing at early stage post-renal transplantation is unknown. We investigated the influence of polymorphisms over time. An initial oral dose of modified-release once-daily tacrolimus formulation (0.20 mg/kg) was administered to 50 Japanese renal transplant patients every 24 h. Stepwise multiple linear regression analysis for tacrolimus dosing was performed each week to determine the effect of patient clinical characteristics. The dose-adjusted trough concentration was approximately 70% higher for patients with the CYP3A5*3/*3 than patients with the CYP3A5*1 allele before the second pre-transplantation tacrolimus dose (0.97 (0.78–1.17) vs. 0.59 (0.45–0.87) ng/mL/mg; p < 0.001). The contribution of genetic factors (CYP3A5*1 or *3) for tacrolimus dosing showed increased variation from Day 14 to Day 28 after transplantation: 7.2%, 18.4% and 19.5% on Days 14, 21 and 28, respectively. The influence of CYP3A5 polymorphisms on the tacrolimus maintenance dosage became evident after Day 14 post-transplantation, although the tacrolimus dosage was determined based only on patient body weight for the first three days after surgery. Tacrolimus dosage starting with the initial administration should be individualized using the CYP3A5 genotype information.
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影响因子：
6.2
作者：
Jacobson PA;Oetting WS;Brearley AM;Leduc R;Guan W;Schladt D;Matas AJ;Lamba V;Julian BA;Mannon RB;Israni A;DeKAF Investigators
通讯作者：
DeKAF Investigators
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作者：
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通讯作者：
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作者：
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通讯作者：
Satoh, Shigeru
影响因子：
6.2
作者：
Niioka, Takenori;Satoh, Shigeru;Miura, Masatomo
通讯作者：
Miura, Masatomo
影响因子：
6.2
作者：
Tsuchiya, N;Satoh, S;Kato, T
通讯作者：
Kato, T