权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

Model-Informed Evaluation of Hydroxyurea Exposure in Special Populations

特殊人群羟基脲暴露的模型知情评估

基本信息

批准号：
10427738
负责人：
Min Dong
金额：
$ 12.7万
依托单位：
CINCINNATI CHILDRENS HOSP MED CTR
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：
2022-06-24 至 2027-03-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10427738
关键词：
Address Affect African Age-Months American Animal Model Breast Feeding Caring Cessation of life Child Childhood Chronic Disease Clinical Clinical Pharmacology Clinical Trials Congenital Abnormality Coupled Data Development Disease Dose Drug Evaluation Drug Exposure Drug Kinetics Electronic Health Record Embryo Ethics Evaluation Exposure to Fetal Hemoglobin Fetus First Pregnancy Trimester Fostering Foundations Funding Future Genetic Diseases Goals Growth Hematologist Human Human Milk Infant Infant Health Interdisciplinary Study International Knowledge Laboratories Lactation Literature Maternal Health Medical Medical center Medicine Mentored Research Scientist Development Award Mentors Mentorship Minority Groups Modeling Mothers Neonatal Newborn Infant Organ Outcome Pain Patients Pediatric Hospitals Pharmaceutical Preparations Pharmacology Pharmacotherapy Physiological Physiology Population Positioning Attribute Postpartum Period Pregnancy Pregnant Women Recommendation Renal function Reproductive Health Research Research Design Research Personnel Research Project Grants Research Proposals Risk Safety Scientist Sickle Cell Sickle Cell Anemia Solid Special Population Stroke System Techniques Teratogens Time Toxic effect Training Training Programs United States National Institutes of Health Visual Vulnerable Populations Weight Woman appropriate dose base breastfed newborn career career development chemical property clinical decision support design dosage dose individualization drug disposition embryo/fetus experience fetal health disparity hydroxyurea improved in silico individual patient innovation interest malformation maternal morbidity mortality neonatal exposure neonate patient health information perinatal morbidity pharmacokinetic model placental transfer pregnant premature prenatal exposure prevent professor research study skills support tools teratogenesis tool tool development

项目摘要

PROJECT SUMMARY/ABSTRACT This K01 application describes a 5-year training plan designed to support Dr. Dong to gain additional skill and knowledge to transition to a special research niche of understanding pharmacotherapy during pregnancy and lactation. Dr. Dong is an Assistant Professor in the Division of Clinical Pharmacology at Cincinnati Children’s Hospital Medical Center (CCHMC). The designed study will leverage her research expertise in pharmacokinetic (PK) modeling coupled with a world renowned research center on sickle cell anemia (SCA) and hydroxyurea pharmacotherapy at CCHMC. SCA is one of the most common genetic disorders affecting millions worldwide. Improvements in medical care have transitioned SCA from a disease of childhood into a long-term chronic illness, and reproductive health has emerged as a significant component in SCA care. Hydroxyurea is an effective and safe pharmacotherapy to ameliorate the clinical course of SCA. However, concerns of toxic effects on fetuses and neonates have limited the use of hydroxyurea in pregnant or lactating women. Without providing continuous management, patients with SCA may develop severe complications such as pain crisis and stroke during pregnancy and postpartum period. So far, no clinical trials could be conducted in these vulnerable populations due to ethical constraints, and significant knowledge gaps remain in our understanding of hydroxyurea placental transfer in humans and its exposure in the fetus and breastfed babies. In recent years, in silico physiologically- based pharmacokinetic (PBPK) modeling has emerged as a powerful tool to predict the drug disposition during pregnancy and postpartum. The overall goal of this proposal is to evaluate hydroxyurea exposure in both mother and fetus/infant during pregnancy and lactation using whole body PBPK modeling. This proposal represents a step forward of using an innovative approach to address health disparities by improving maternal and infant health outcomes in minority populations. The study includes the following Specific Aims: 1) To quantify hydroxyurea exposure in pregnant women and the embryo/fetus using integrated PBPK models; 2) To assess hydroxyurea exposure in breastfeeding newborns and infants with integrated PBPK models; 3) To develop a clinical decision support tool in the prediction of hydroxyurea exposure in individual patients. The training goal of this K01 award is to foster Dr. Dong’s career growth to become a successful, independent, NIH funded scientist who has the expertise in whole body maternal/fetal/lactation/neonatal drug evaluation using an in silico PBPK approach and in decision support tool development. Dr. Dong will receive training from an outstanding mentorship team led by her primary mentor Dr. Vinks, an expert in quantitative clinical pharmacology, and co- mentor Dr. Ware, a highly accomplished hematologist who has led many international research efforts in hydroxyurea treatment and SCA care improvement. This mentoring team in concert with a balanced training program and excellent research project will provide a solid foundation to Dr. Dong’s career development in the field of hydroxyurea research and PBPK modeling for special populations.

项目总结/文摘