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

跨性别成人药物代谢和转运改变的激素介导机制

• 批准号: 10506038
• 负责人: Lauren Cirrincione
• 金额: $ 18.71万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-08-01 至 2026-07-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10506038
• 关键词: ABCB1 gene; Address; Adult; Anti-HIV Therapy; Area; Award; Birth; CYP3A4 gene; Cardiovascular system; Caring; Chronic Disease; Clinic; Clinical; Clinical Pharmacology; Complex; Creatinine clearance measurement; Cytochrome P450; Data; Digoxin; Doctor of Pharmacy; Dose; Drug Interactions; Drug Prescriptions; Drug Transport; Endocrinology; Enrollment; Environment; Enzymes; Estradiol; Estrogen Therapy; Estrogens; Faculty; Fellowship; Female; Funding; Gender; Gender Identity; Gender Role; Goals; Gonadal Steroid Hormones; Grant; HIV; HIV Infections; Hepatic; Hormonal; Hormones; Hour; Human; In Vitro; Injectable; International; Intestines; Intravenous; Kidney; Learning; Longitudinal Studies; Mediating; Medical; Medicine; Mental Health Services; Mentored Patient-Oriented Research Career Development Award; Mentorship; Methods; Midazolam; Modeling; Oral; Outcome; Participant; Pathway interactions; Patients; Persons; Pharmaceutical Preparations; Pharmacology; Pharmacology Study; Pharmacy Schools; Physiological; Plasma; Population; Postpartum Period; Pregnancy; Pregnant Women; Procedures; Proteins; Public Health; Regulation; Research; Research Design; Research Personnel; Research Proposals; Role; Safety; Sampling; Sex Characteristics; Testing; Time; Toxic effect; Training; United States National Institutes of Health; Universities; Urine; Variant; Visit; Washington; Weight; arm; base; burden of illness; career; career development; clinically significant; cytochrome P450 3A; design; drug disposition; drug efficacy; drug metabolism; experimental study; faculty mentor; hormone therapy; in vivo; infection burden; inter-individual variation; liquid chromatography mass spectrometry; male; medication safety; member; patient population; professor; programs; prospective; protein biomarkers; routine therapy; sample collection; skills; statistics; transgender; transgender women; translational scientist; urinary

PROJECT SUMMARY/ABSTRACT Dr. Lauren Cirrincione, an Assistant Professor at the University of Washington School of Pharmacy, is applying for a K23 award. She completed a PharmD and clinical HIV pharmacology fellowship, and she is a tenure- eligible faculty member at the University of Washington School of Pharmacy. She is awarded a start-up package and 9-person months of protected time and is working to establish herself as a clinical translational investigator in clinical pharmacology of transgender medicine. 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 K23 grant will provide: (1) expertise in probe substrate study methods and analysis and (2) longitudinal study design in transgender adults and (3) training in skills needed to become an independent NIH-funded investigator with expertise in hormone mediated mechanisms of altered drug disposition. To achieve these goals, Dr. Cirrincione's mentorship and research team consists of internationally recognized experts in clinical pharmacology, endocrinology, and statistics who will support the proposed training plan and research proposal. All faculty mentors have a strong track record of mentorship, know Dr. Cirrincione well, have established collaborative research programs, and will assist Dr. Cirrincione in career development. Training and research will occur at the University of Washington, a global leader in research and strong environment to support early career investigators develop into independently funded investigators. This proposal addresses an important gap in transgender medicine, specifically whether high-dose sex hormone therapy alters the disposition of other prescribed drugs. We propose to study 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.

项目摘要/摘要 华盛顿大学药学院的助理教授Lauren Cirrincione博士正在申请 获得K23奖。她完成了PharmD和临床HIV药理学奖学金，她是一个终身制 - 华盛顿大学药学院的合格教师。她被授予初创企业 包装和9人的保护时间，并正在努力将自己确立为临床翻译 跨性别医学临床药理学研究者。 Cirrincione博士的职业目标包括 对跨性别和性别多样的马酮介导的药物相互作用的领域的重要贡献 成人，专门将临床药理学应用于跨性别医学。这项K23赠款将提供：（1） 探针底物研究方法和分析方面的专业知识以及（2）变性者的纵向研究设计 成人和（3）技能培训需要成为一名具有专业知识的独立NIH资助的研究者 激素介导的药物处置机制。为了实现这些目标，Cirrincione博士 Menorship和Research团队由国际认可的临床药理学专家组成， 内分泌学以及将支持拟议的培训计划和研究建议的统计数据。所有教师 认识Cirrincione博士，导师的指导记录很强，已经建立了合作 研究计划，并将帮助Cirrincione博士进行职业发展。培训和研究将发生在 华盛顿大学是研究和强大环境的全球领导者，以支持早期职业 调查人员发展成独立资助的研究人员。该提议解决了一个重要的差距 跨性别医学，特别是高剂量性骑马治疗是否改变了其他 处方药。我们建议研究探针底物→生物标志物→蛋白质活性框架以测试 在体内雌二醇治疗之前和期间，主要药物处理蛋白质的差异。 Cirrincione Will博士 在跨性别成年人进行机械，临床药理学研究方面获得专业知识。生成的数据 该建议将用于推进临床策略以克服药物安全和效率的变化 在跨性别成年人中，增加体内机械数据可用的可用性以确立性恐怖的作用 在药物处置途径上。