Pasternak Amy L, Kidwell Kelley M, Dempsey Jacqueline M, Gersch Christina L, Pesch Andrea, Sun Yihan, Rae James M, Hertz Daniel L, Park Jeong M
Department of Clinical Pharmacy, University of Michigan College of Pharmacy, Ann Arbor, MI 48109, USA.
Department of Biostatistics, University of Michigan School of Public Health, Ann Arbor, MI 48109, USA.
Pharmacogenomics. 2019 Apr;20(6):421-432. doi: 10.2217/pgs-2019-0002. Epub 2019 Apr 15.
This study evaluated the impact of genotype and other patient characteristics on sublingual (SL) tacrolimus exposure and compared the relationship with oral administration. Tacrolimus concentrations were retrospectively collected for adult lung transplant recipients, who were genotyped for , , , and . Regression analyses were performed to determine covariates that impacted the SL and oral tacrolimus concentration/dose ratios. An interaction of genotype and CYP3A inhibitor increased the SL concentration/dose, while cystic fibrosis decreased the SL concentration/dose. The oral concentration/dose was independently associated with these covariates and was increased by serum creatinine and number of tacrolimus doses. This study suggests personalized dosing strategies for tacrolimus likely need to consider characteristics beyond genotype.
本研究评估了基因型及其他患者特征对舌下（SL）他克莫司暴露量的影响，并比较了其与口服给药的关系。回顾性收集成年肺移植受者的他克莫司浓度，这些受者进行了 、 、 及 的基因分型。进行回归分析以确定影响 SL 和口服他克莫司浓度/剂量比的协变量。 基因型与 CYP3A 抑制剂的相互作用增加了 SL 浓度/剂量，而囊性纤维化则降低了 SL 浓度/剂量。口服浓度/剂量与这些协变量独立相关，并因血清肌酐和他克莫司剂量数而增加。本研究表明，他克莫司的个性化给药策略可能需要考虑 基因型以外的特征。
