Hormone mediated mechanisms of altered drug metabolism and transport in transgender adults

华盛顿大学药学院助理教授劳伦·奇林西奥内博士正在申请K23奖项。Cirricione博士的职业目标包括在跨性别者和不同性别成年人的荷尔蒙调节药物相互作用领域做出重大贡献，特别是将临床药理学应用于变性人医学。这笔赠款将提供1.探测底物研究方法和分析方面的专业知识，2.纵向研究设计和3.培训，以成为NIH资助的独立研究人员，在激素调节的药物处置机制方面具有专业知识，并将解决高剂量性激素治疗是否改变其他处方药的处置问题。我们将使用探针底物-生物标记物-蛋白质活性框架来测试体内雌激素治疗前和治疗期间主要药物处理蛋白的差异。西林西翁博士将获得在变性人成人身上进行机械性临床药理学研究的专业知识。这项提案产生的数据将被用于推进临床策略，以克服变性人成人药物安全性和有效性的变化，并增加可用的体内机制数据，以确定性激素在药物处置途径中的作用。

Dr. Lauren Cirrincione, an Assistant Professor at the University of Washington School of Pharmacy, is applying for a K23 award. Dr. Cirrincione’s career goals include making significant contributions to the field of hormone mediated drug interactions in transgender and gender diverse adults, specifically applying clinical pharmacology to transgender medicine. This grant will provide 1. expertise in probe substrate study methods and analysis and 2. longitudinal study design and 3. training to become an independent NIH-funded investigator with expertise in hormone mediated mechanisms of altered drug disposition and will address whether high-dose sex hormone therapy alters the disposition of other prescribed drugs. We will use a probe substrate-biomarker-protein activity framework to test differences in major drug handling proteins before and during estradiol treatment in vivo. Dr. Cirrincione will gain expertise in conducting mechanistic, clinical pharmacology studies in transgender adults. Data generated from this proposal will be used to advance clinical strategies to overcome changes in drug safety and efficacy in transgender adults and to increase available in vivo mechanistic data to establish the role of sex hormones on pathways of drug disposition.