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

基本信息

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
项目类别：
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

项目摘要

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.

项目概要/摘要华盛顿大学药学院助理教授 Lauren Cirrincione 博士正在申请她获得了 K23 奖，并完成了药学博士和临床 HIV 药理学奖学金，并且是终身教授。她是华盛顿大学药学院的合格教师，被授予初创企业称号。套餐和 9 人月的受保护时间，并正在努力将自己打造成临床转化人员 Cirrincione 博士是跨性别医学临床药理学研究者，其职业目标包括：对跨性别者和性别多样化的激素介导的药物相互作用领域做出了重大贡献成人，特别是将临床药理学应用于跨性别医学。这项 K23 拨款将提供：(1) 探针底物研究方法和分析方面的专业知识以及（2）跨性别者的纵向研究设计成人和 (3) 成为 NIH 资助的独立调查员所需的技能培训为了实现这些目标，Cirrincione 博士提出了激素介导的药物处置机制。导师和研究团队由国际公认的临床药理学专家组成，内分泌学和统计学将支持拟议的培训计划和研究提案的所有教员。导师们拥有良好的指导记录，非常了解 Cirrincione 博士，并建立了合作关系研究计划，并将协助 Cirrincione 博士进行职业发展。培训和研究将在以下地点进行。华盛顿大学，研究领域的全球领先者和支持早期职业的强大环境该提案解决了研究人员发展为独立资助的研究人员的一个重要差距。跨性别医学，特别是高剂量性激素治疗是否会改变其他人的性格我们提出药物来研究探针底物→生物标志物→蛋白质活性框架以进行测试。 Cirrincione 博士将研究体内雌二醇治疗之前和期间主要药物处理蛋白的差异。获得对跨性别成人进行机械、临床药理学研究的专业知识生成的数据。该提案中的内容将用于推进临床策略，以克服药物安全性和有效性的变化在跨性别成人中，并增加可用的体内机制数据以确定性激素的作用关于药物处置途径。