Almeida-Paulo G N, Dapía García I, Lubomirov R, Borobia A M, Alonso-Sánchez N L, Espinosa L, Carcas-Sansuán A J
Department of Clinical Pharmacology, La Paz University Hospital, School of Medicine, Universidad Autónoma de Madrid, IdiPAZ, Madrid, Spain.
Instituto de Genética Médica y Molecular (INGEMM), La Paz University Hospital, Universidad Autónoma de Madrid, IdiPAZ, Madrid, Spain.
Pharmacogenomics J. 2018 Jan;18(1):180-186. doi: 10.1038/tpj.2016.93. Epub 2017 Jan 17.
Tacrolimus (TAC) is highly effective for the prevention of acute organ rejection. However, its clinical use may be challenging due to its large interindividual pharmacokinetic variability, which can be partially explained by genetic variations in TAC-metabolizing enzymes and transporters. The aim of this study was to evaluate the influence of genetic and clinical factors on TAC pharmacokinetic variability in 21 stable pediatric renal transplant patients. This study was nested in a previous Prograf to Advagraf conversion clinical trial. CYP3A5, ABCB1 and two POR genotypes were assessed by real-time PCR. The impact on TAC pharmacokinetics of individual genetic variants on CYP3A5 nonexpressors was evaluated by genetic score. Explicative models for TAC AUC C and C after Advagraf were developed by linear regression. The built genetic scores explain 13.7 and 26.5% of the total AUC and C total variability, respectively. Patients genetic information should be considered to monitorizate and predict TAC exposure.
他克莫司（TAC）在预防急性器官排斥反应方面非常有效。然而，由于其个体间药代动力学变异性大，其临床应用可能具有挑战性，TAC代谢酶和转运体的基因变异可部分解释这种变异性。本研究的目的是评估基因和临床因素对21例稳定的小儿肾移植患者TAC药代动力学变异性的影响。本研究嵌套于先前的普乐可复至新山地明转换临床试验中。通过实时PCR评估CYP3A5、ABCB1和两种POR基因型。通过基因评分评估个体基因变异对CYP3A5非表达者TAC药代动力学的影响。通过线性回归建立了新山地明治疗后TAC AUC和C的解释模型。构建的基因评分分别解释了总AUC和C总变异性的13.7%和26.5%。应考虑患者的基因信息来监测和预测TAC暴露情况。
