Department of Surgery, Division of Transplantation, Medical University Graz, Graz, Austria.
Clin Transplant. 2011 Jan-Feb;25(1):146-50. doi: 10.1111/j.1399-0012.2009.01198.x.
tacrolimus and everolimus are immunosuppressive drugs metabolized by enzymes of the CYP3A subfamily. A common variant of the CYP3A5 gene, CYP3A53, results in strongly decreased CYP3A5 activity and has been shown to influence Tacrolimus blood concentrations, but its role for the pharmacogenetics of Everolimus remains unclear. Aim of the study was to examine the role of CYP3A53 variant in tacrolimus and everolimus dose and drug levels after heart transplantation.
The present study comprised 15 patients with Tacrolimus and 30 patients with Everolimus-based maintenance therapy after heart transplantation. CYP3A5 genotypes were determined and correlated with clinical data.
In the Tacrolimus group, 13 subjects were CYP3A5 non-expressors (*3/*3 genotype) and two were heterozygous expressors (*1/*3 genotype). Average Tacrolimus dose was significantly higher in subjects expressing CYP3A5 compared to non-expressors. Tacrolimus levels were not significantly different at any point of time. In the Everolimus group, 27 subjects were CYP3A5 non-expressors (*3/*3 genotype) and three were heterozygous expressors (*1/*3). Neither Everolimus dose nor levels were significantly different between CYP3A5 expressors and non-expressors at any point of time.
We conclude that in adult patients after heart transplantation, CYP3A5 genotypes have a strong influence on Tacrolimus, but not Everolimus dose requirement.
他克莫司和依维莫司是经 CYP3A 亚家族酶代谢的免疫抑制剂药物。CYP3A5 基因的常见变体 CYP3A53 导致 CYP3A5 活性显著降低，并已被证明会影响他克莫司的血药浓度，但它在依维莫司药物遗传学中的作用尚不清楚。本研究的目的是研究 CYP3A53 变体在心移植后他克莫司和依维莫司剂量和药物水平中的作用。
本研究包括 15 例接受他克莫司和 30 例接受依维莫司维持治疗的心移植患者。确定了 CYP3A5 基因型，并与临床数据相关联。
在他克莫司组中，13 例受试者为 CYP3A5 无表达者（*3/*3 基因型），2 例为杂合表达者（*1/*3 基因型）。表达 CYP3A5 的受试者的他克莫司剂量明显高于不表达者。在任何时间点，他克莫司水平均无显著差异。在依维莫司组中，27 例受试者为 CYP3A5 无表达者（*3/*3 基因型），3 例为杂合表达者（*1/*3 基因型）。在任何时间点，CYP3A5 表达者和不表达者之间的依维莫司剂量或水平均无显著差异。
我们的结论是，在成年心脏移植患者中，CYP3A5 基因型对他克莫司有很强的影响，但对依维莫司的剂量需求没有影响。
