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（由申请方提供）：本申请的目的和长期目标是通过产前皮质类固醇治疗个体化优化孕产妇和新生儿结局。我们假设，通过更好地了解产前皮质类固醇的分布和作用，我们将能够为BMZ制定个性化的给药策略，以改善新生儿结局和安全性。本研究的目的是充分询问BMZ的处置、疗效和安全性，以改善其治疗用途并解决疗效差异。我们将通过两个具体目标来实现这一目标：1）我们将描述可能导致产前皮质类固醇反应改变新生儿结局的药代动力学和药物遗传学变化; 2）我们将开发一种新的个性化治疗模式，旨在减少差异并优化新生儿结局。一个具有完成这些研究所需的必要专门知识的多学科协作研究小组已经到位。为了实现这些目标，我们将利用我们成功的受试者招募基础设施，招募一组因预期早产而接受BMZ治疗的女性。该研究将产生旨在最大限度地提高BMZ对新生儿益处的数据。然后可以在临床试验中验证和测试创建的个性化治疗模型。这种个体化治疗方法将对大量早产婴儿的治疗产生重大影响，这些婴儿可能无法通过当前的剂量标准进行充分治疗。该提案是创新的，因为它将是第一个产科药代动力学/药效学/药物遗传学建模研究，以解决产前皮质类固醇的结果差异，并将联合收割机的遗传数据与药代动力学测量，以更好地了解这些患者的药物反应。这项研究计划也有很大的潜力，作为一个模板，为更明智的个性化药物治疗的调查，为广泛的妊娠条件。