Age and CYP3A5 genotype affect tacrolimus dosing requirements after transplant in pediatric heart recipients.
Age and CYP3A5 genotype affect tacrolimus dosing requirements after transplant in pediatric heart recipients.
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DOI：
10.1016/j.healun.2011.08.001
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发表时间：
2011-12
期刊：
影响因子：
--
通讯作者：
de Wildt SN
中科院分区：
文献类型：
--
作者：
Gijsen V;Mital S;van Schaik RH;Soldin OP;Soldin SJ;van der Heiden IP;Nulman I;Koren G;de Wildt SN
他克莫司是儿童心脏移植中常用的免疫抑制药物之一。在移植后的直接时期，药代动力学存在很大的变化，导致不良事件的风险增加。关于年龄、CYP3A5和ABCB1基因型以及疾病严重程度对儿童心脏移植受者性格和结局变化的相互作用的数据有限。我们研究了年龄与CYP3A5和ABCB1基因型的关系，以及儿童心脏移植后14天他克莫司剂量（mg/kg）、稳态谷浓度、浓度/剂量比的儿童死亡风险（PRISM）评分，以及排斥反应和肾功能的关系。移植后39名儿童（中位年龄6.0岁）接受他克莫司治疗。移植时年龄与他克莫司剂量要求（rs = - 0.447, p = 0.004）和浓度/剂量比（rs = 0.351, p = 0.029）存在相关性。CYP3A5表达者需要更高剂量的他克莫司（0.14 [0.09]vs 0.06 [0.04] mg/kg/12小时，p = 0.001），浓度/剂量比更低（45.34 [44.54]vs 177.78 [145.38] ng/ml / mg/kg/12小时，p < 0.0001）。这种关系在ABCB1基因型中未见。年龄和CYP3A5基因型预测他克莫司给药需求及浓度/剂量比（R2 = 0.351, p = 0.001, R2 = 0.521, p < 0.001）。没有发现任何CYP3A5或ABCB1基因型与肾小球滤过率之间的关系。年龄较小和CYP3A5表达基因型与较高的剂量要求和较低的他克莫司浓度/剂量比独立相关。
Tacrolimus is one of the commonly used immunosuppressive drugs for pediatric heart transplants. Large variation exists in pharmacokinetics during the direct post-transplant period, resulting in an increased risk of adverse events. Limited data are available on the interaction of age, CYP3A5 and ABCB1 genotype, and disease severity on the variation in disposition and outcome in pediatric heart transplant recipients. We studied the relationship between age and CYP3A5 and ABCB1 genotype and the Pediatric Risk of Mortality (PRISM) score on tacrolimus dose (mg/kg), steady-state trough concentrations, and concentration/dose ratio, as well as rejection and renal function for 14 days after heart transplant in children. Tacrolimus was administered to 39 children (median age, 6.0 years) after transplant. A correlation was found between the age at the time of transplant and the tacrolimus dosing requirements (rs = −0.447, p = 0.004) and the concentration/dose ratio (rs = 0.351, p = 0.029). CYP3A5 expressors required median (interquartile range) higher doses of tacrolimus (0.14 [0.09] vs 0.06 [0.04] mg/kg/12 hours, p = 0.001), and had lower concentration/dose ratios (45.34 [44.54] vs 177.78 [145.38] ng/ml per mg/kg/12 hours, p < 0.0001). This relationship was not seen with the ABCB1 genotype. Age and CYP3A5 genotype predicted the tacrolimus dosing requirements as well as the concentration/dose ratio (R2 = 0.351, p = 0.001 and R2 = 0.521, p < 0.001). No relationship was found between any of the CYP3A5 or ABCB1 genotypes and the estimated glomerular filtration rate. Younger age and CYP3A5 expressor genotype were independently associated with higher dosing requirements and lower tacrolimus concentration/dose ratios.
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影响因子：
1.3
作者：
MacFarlane, GD;Venkataramanan, R;Fitzsimmons, WE
通讯作者：
Fitzsimmons, WE
DOI：
10.1097/01.fpc.0000114747.08559.49
发表时间：
2004-07-01
期刊：
PHARMACOGENETICS
影响因子：
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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：
van Gelder, T
影响因子：
6.7
作者：
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通讯作者：
Inui, Ken-ichi
影响因子：
2.5
作者：
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通讯作者：
Levine, Marc