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: 9888973
• 负责人: DAVID M. HAAS
• 金额: $ 41.35万
• 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 2022-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9888973
• 关键词: Address; Adrenal Cortex Hormones; Advocate; Affect; Betamethasone; Biological Markers; Birth Weight; Clinical; Clinical Trials; Data; Development; Discipline of obstetrics; Dose; Drug Kinetics; Exposure to; Foundations; Genetic; Genetic Polymorphism; Genotype; Gestational Age; Goals; Infrastructure; Interdisciplinary Study; Intervention; Investigation; Lead; Life; Measurement; Modeling; Neonatal; Neonatal Mortality; Obesity Epidemic; Obstetric Fetal Pharmacology; Outcome; Participant; Pathway interactions; Patients; Pharmaceutical Preparations; Pharmacodynamics; Pharmacogenetics; Pharmacology; Pharmacotherapy; Population Heterogeneity; Pregnancy; Pregnant Women; Premature Birth; Premature Infant; Prevention; Public Health; Regimen; Research; Risk; Safety; Savings; Schedule; Scourge; Steroids; Study models; Testing; Therapeutic; Therapeutic Uses; United States; Variant; Woman; Work; adverse outcome; antenatal; antenatal care; cohort; disparity reduction; dose individualization; ethnic difference; improved; innovation; maternal outcome; neonatal morbidity; neonatal outcome; neonatal respiratory distress; neonate; novel; offspring; personalized approach; personalized medicine; personalized therapeutic; pharmacokinetic model; pharmacokinetics and pharmacodynamics; predictive modeling; premature; programs; public health relevance; randomized trial; recruit; respiratory; respiratory distress syndrome; response; sociodemographic factors; 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.

 描述（由应用程序提供）：本应用的目的和长期目标是通过个体化静脉皮质类固醇治疗来优化母体和新生儿结局。我们的重点是替他米松（BMZ），我们假设通过更好地理解静脉皮质类固醇的处置和作用，我们将能够为BMZ制定个性化的剂量策略，以改善新生儿的结果和安全性。这项研究的目的是完全询问BMZ的处置，有效性和安全性，以改善其治疗用途的解决有效性差异。我们将通过两个具体的目标来实现这一点：1）我们将表征药代动力学和药物遗传学变异，这些变异可能导致对静脉皮质类固醇的响应而导致新生儿结局的改变； 2）我们将开发一种新型的个性化治疗模型，旨在减少差异和优化新生儿结果。拥有完成这些研究所需的必要专业知识的协作多学科研究团队已就位。为了实现这些目标，我们将利用我们成功的受试者招聘基础设施来招募因预期早产而进行BMZ治疗的一群女性。该研究将生成旨在最大化BMZ的新生儿益处的数据。然后，可以在临床试验中对创建的个性化治疗模型进行验证和测试。这种个性化的治疗方法将对出生的大量婴儿的治疗产生重大影响。该提案具有创新性，因为它将是最早的产科药代动力学/药效/药物遗传学建模研究，可以解决来自静脉皮质类固醇的结果分布，并将遗传数据与药代动力学测量相结合，以便在这些患者中更好地了解这些患者的药物反应。该研究计划还具有巨大的潜力，可以作为模板，用于在广泛的怀孕条件下进行更明智的个性化药物治疗研究。