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群体规模生物样本库中实体器官移植受者对药物遗传学药物的可操作暴露率

Prevalence of Actionable Exposures to Pharmacogenetic Medications Among Solid Organ Transplant Recipients in a Population-Scale Biobank.

作者信息

Radwan Alaa, Deininger Kimberly M, Ambardekar Amrut V, Anderson Heather D, Rafaels Nicholas, Saba Laura M, Aquilante Christina L

机构信息

Department of Pharmaceutical Sciences, University of Colorado Skaggs School of Pharmacy and Pharmaceutical Sciences, Aurora, CO 80045, USA.

Colorado Center for Personalized Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA.

出版信息

J Pers Med. 2025 May 2;15(5):185. doi: 10.3390/jpm15050185.

Abstract

: Solid organ transplant (SOT) recipients are exposed to multiple medications, many of which have pharmacogenetic (PGx) prescribing recommendations. This study leveraged data from a population-scale biobank and an enterprise data warehouse to determine the prevalence of actionable exposures to PGx medications among kidney, heart, and lung transplant recipients during the first six months post-transplant. : We conducted a retrospective analysis of adult SOT patients with genetic data available from the Colorado Center for Personalized Medicine (CCPM) biobank and clinical data from Health Data Compass (HDC). We evaluated 29 variants in 13 pharmacogenes and 42 Clinical Pharmacogenetics Implementation Consortium (CPIC) level A or B medications (i.e., sufficient evidence to recommend at least one prescribing action based on genetics). The primary outcome was actionable exposure to a PGx medication (i.e., actionable phenotype and a prescription for an affected PGx medication). : The study included 358 patients. All patients were prescribed at least one PGx medication, and 49.4% had at least one actionable exposure to a PGx medication during the first six months post-transplant. The frequency of actionable exposure was highest for tacrolimus (15.4%), followed by proton pump inhibitors (PPIs) (15.1%) and statins (12.8%). Statin actionable exposures significantly differed by transplant type, likely due to variations in prescribing patterns and actionable phenotypes for individual statins. : Our findings highlight the potential clinical utility of PGx testing among SOT patients. Further studies are needed to address the impact on clinical outcomes and the optimal timing of PGx testing in the SOT population.

摘要

实体器官移植(SOT)受者会接触多种药物,其中许多药物都有药物遗传学(PGx)处方建议。本研究利用来自人群规模生物样本库和企业数据仓库的数据,以确定肾、心和肺移植受者在移植后前六个月内可采取行动的PGx药物暴露率。

我们对来自科罗拉多个性化医学中心(CCPM)生物样本库的有基因数据的成年SOT患者以及来自健康数据指南针(HDC)的临床数据进行了回顾性分析。我们评估了13个药物基因中的29个变异以及42种临床药物遗传学实施联盟(CPIC)A级或B级药物(即有足够证据基于遗传学推荐至少一种处方行动)。主要结局是可采取行动的PGx药物暴露(即可采取行动的表型和针对受影响的PGx药物的处方)。

该研究纳入了358名患者。所有患者都至少开具了一种PGx药物,49.4%的患者在移植后前六个月内至少有一次可采取行动的PGx药物暴露。他克莫司的可采取行动暴露频率最高(15.4%),其次是质子泵抑制剂(PPI)(15.1%)和他汀类药物(12.8%)。他汀类药物的可采取行动暴露因移植类型而异,这可能是由于个体他汀类药物的处方模式和可采取行动表型存在差异。

我们的研究结果突出了PGx检测在SOT患者中的潜在临床应用价值。需要进一步研究以解决其对临床结局的影响以及SOT人群中PGx检测的最佳时机。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/eeb6/12113073/c6a57f30d5e6/jpm-15-00185-g001.jpg

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