Pharmacokinetics and modeling of betamethasone therapy in threatened preterm birth

先兆早产倍他米松治疗的药代动力学和模型

• 批准号: 9123871
• 负责人: DAVID M. HAAS
• 金额: $ 46.18万
• 依托单位: INDIANA UNIV-PURDUE UNIV AT INDIANAPOLIS
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-03-01 至 2021-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9123871
• 关键词: Address; Adrenal Cortex Hormones; Advocate; Affect; Betamethasone; Biological Markers; Birth Weight; Clinical; Clinical Trials; Data; Demographic Factors; Development; Discipline of obstetrics; Dose; Drug Kinetics; Epidemic; Exposure to; Foundations; Genetic; Genetic Polymorphism; Genotype; Gestational Age; Goals; Interdisciplinary Study; Intervention; Investigation; Lead; Life; Measurement; Modeling; Neonatal; Neonatal Mortality; Obesity; Obstetric Fetal Pharmacology; Outcome; Participant; Pathway interactions; Patients; Pharmaceutical Preparations; Pharmacodynamics; Pharmacogenetics; Pharmacotherapy; Population Heterogeneity; Pregnancy; Pregnant Women; Premature Birth; Premature Infant; Prevention; Public Health; Recruitment Activity; Regimen; Research; Research Infrastructure; Risk; Safety; Schedule; Scourge; Steroids; Study models; Testing; Therapeutic; Therapeutic Uses; United States; Variant; Woman; Work; adverse outcome; cohort; disparity reduction; ethnic difference; genetic analysis; improved; innovation; neonatal morbidity; neonatal outcome; neonatal respiratory distress; neonate; novel; offspring; personalized approach; personalized medicine; personalized therapeutic; pharmacokinetic model; predictive modeling; premature; programs; public health relevance; randomized trial; respiratory; respiratory distress syndrome; response; standard of care

 DESCRIPTION (provided by applicant): The purpose and long-term goal of this application is to optimize maternal and neonatal outcomes by individualizing antenatal corticosteroid therapy. Focusing on betamethasone (BMZ), we hypothesize that by better understanding the disposition and action of antenatal corticosteroids, we will be able to develop an individualized dosing strategy for BMZ that will improve neonatal outcomes and safety. The objective of this study is to fully interrogate the disposition, efficacy, and safety of BMZ to improve its therapeutic use an resolve efficacy discrepancies. We will accomplish this through two specific aims: 1) We will characterize the pharmacokinetics and the pharmacogenetic variations that may lead to altered neonatal outcomes in response to antenatal corticosteroids; and 2) We will develop a novel personalized therapeutic model aimed at reducing disparities and optimizing neonatal outcomes. A collaborative multidisciplinary research team with the necessary expertise required to complete these studies is in place. To accomplish these aims we will utilize our successful subject recruitment infrastructure to recruit a cohort of women presenting for BMZ therapy due to anticipated preterm birth. The research will generate data aimed at maximizing the neonatal benefits from BMZ. The individualized therapeutic model created then can be validated and tested in a clinical trial. This individualized approach to treatment would have a significant impact on the therapy of a large number of babies born prematurely who may be inadequately treated by the current dosing standard. The proposal is innovative in that it would be one of the first obstetric pharmacokinetic/pharmacodynamic/pharmacogenetic modeling studies to address outcome disparities from antenatal corticosteroids and would combine the genetic data with pharmacokinetic measurements to allow better understanding of the drug response in these patients. This program of research also has great potential to serve as a template for more informed individualized pharmacotherapy investigations for a wide range of pregnancy conditions.