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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：
10657794
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/10657794
关键词：
ABCB1 gene Address Adult Anti-HIV Therapy Area Award 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 Eligibility Determination Endocrinology Enrollment Environment Enzymes Estradiol Estrogen Therapy Estrogens Faculty Fellowship Female Funding 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 assigned male at birth burden of illness career career development clinical translation clinically significant cytochrome P450 3A design drug disposition drug efficacy drug metabolism experimental study faculty mentor gender affirmation gender affirming hormone therapy gender diversity health care service utilization hormone therapy in vivo infection burden inter-individual variation liquid chromatography mass spectrometry 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

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.

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。