Home vs. Clinic Collection of Human Milk in Evaluating the Pharmacokinetics of Four Medications

家庭与诊所收集母乳评估四种药物的药代动力学

• 批准号: 10300576
• 负责人: CHRISTINA CHAMBERS
• 金额: $ 19.64万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN DIEGO
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-11-15 至 2024-10-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10300576
• 关键词: Address; Aliquot; Area; Blood; Blood specimen; Breast Feeding; Child; Childhood; Clinic; Clinic Visits; Clinical; Clinical Trials; Cognitive; Collaborations; Collection; Counseling; Data; Doctor of Philosophy; Drug Exposure; Drug Kinetics; Drug Prescriptions; Enrollment; Environment; Epidemiologist; European; European Union; Exposure to; Future; Goals; Gold; Health Benefit; Home; Home environment; Human Milk; Infrastructure; Instruction; Interdisciplinary Study; Laboratories; Lactation; Logistics; Measurable; Methods; Milk; Modeling; Mothers; National Institute of Child Health and Human Development; Oxycodone; Patients; Perinatal; Persons; Pharmaceutical Preparations; Pharmacologic Substance; Pharmacology; Plasma; Population; Prednisone; Pregnancy; Process; Protocols documentation; Provider; Randomized; Recommendation; Recording of previous events; Research; Risk; Ritalin; Safety; Sampling; Science; Sertraline; Ships; Source; Spottings; Temperature; Testing; Therapeutic; Training; Uncertainty; Universities; Utah; Validation; Visit; Woman; base; biobank; cohort; cost; evidence based guidelines; experience; human data; infant nutrition; inter-individual variation; interest; knowledge of results; maternal serum; medication safety; model building; pediatrician; pharmacokinetic model; prenatal; prospective; sample collection; skills

PROJECT SUMMARY Breastfeeding is the recommended primary source of nutrition for infants and has been associated with cognitive and other health benefits for the developing child. An estimated 50-80% of women take prescription medications while breastfeeding, yet only 2% of medications have adequate data for evaluating their safety when used in lactation. This represents a critical gap in knowledge resulting in many women either avoiding necessary medications or discontinuing breastfeeding. The primary barrier to determining the extent of drug passage into breast milk is collecting enough breast milk and blood samples to both quantify drug concentrations and account for inter-individual variability in drug exposure. For numerous reasons, it is often difficult for new mothers to come to study visits. In order to generate much-needed data on drug passage into breast milk, additional methods of sample collection are needed that will enable more lactating women to participate and to generate a sufficient critical mass of data to make strong recommendations on the safety of a given drug while breastfeeding. This proposal will rigorously test the central hypothesis that home collection of human milk and blood samples will be successfully validated against more traditional clinic-based collection methods for pharmacokinetic (PK) studies. Building on the infrastructure of the existing UC San Diego Human Milk Research Biorepository study and a highly qualified, multidisciplinary research team at UC San Diego and the University of Utah, we will enroll 20 breastfeeding women already prescribed either prednisone, oxycodone, sertraline, or methylphenidate, for a total of 80 women. In each medication group, 10 women will be randomly assigned to one of two cohorts. Women in Cohort 1 will present to clinic and provide a breast milk and blood sample that will be split into two aliquots. Aliquot 1 will be processed and stored under rigorous study collection conditions. Aliquot 2 will be processed and stored under mimicked home collection conditions. Storing the same sample under different conditions will allow comparison of home collection to the gold standard of clinic collection. The data collected from Cohort 1 will be combined with existing PK data from a collaborating network to build population PK models. These PK models will be used to generate model-predicted concentrations that will be compared with home-collected concentrations from Cohort 2. Women in Cohort 2 will be provided instructions and supplies for home collection of breast milk and dried blood spot samples that will be shipped to UC San Diego. Concentrations from home- collected samples will be compared to model-predicted concentrations from the PK models generated above. By successfully validating methods for home collections, the proposed research will transform the study of drug passage into breast milk by dramatically expanding the number of women who can participate, ultimately leading to an exponential increase in the number of medications for which there is adequate lactation safety data. The methods developed in this R21 proposal will be used to inform a large prospective, opportunistic trial of multiple drugs across numerous therapeutic areas and will involve collaboration with large US and European networks.

项目摘要 母乳喂养是婴儿推荐的主要营养来源， 和其他健康益处。据估计，50-80%的女性服用处方药。 虽然母乳喂养，但只有2%的药物有足够的数据来评估其安全性时， 哺乳期这是一个关键的知识差距，导致许多妇女要么避免必要的 药物或停止母乳喂养。确定药物进入的程度的主要障碍 母乳是收集足够的母乳和血液样本，以量化药物浓度和帐户 药物暴露的个体间差异。由于种种原因，新妈妈们通常很难来 学习访问。为了产生急需的关于药物进入母乳的数据，还需要其他方法， 需要收集样本，使更多的哺乳期妇女能够参与，并产生足够的 关键的大量数据，以便对母乳喂养期间给定药物的安全性提出强有力的建议。 这项提案将严格检验中心假设，即家庭收集母乳和血液样本， 将成功验证更传统的基于临床的药代动力学（PK）采集方法 问题研究建立在现有的加州大学圣地亚哥分校人乳研究生物储存库研究的基础设施上 以及加州大学圣地亚哥分校和犹他州大学的一支高素质的多学科研究团队，我们将招收 20名母乳喂养的妇女已经开了强的松、羟考酮、舍曲林或哌甲酯， 共80名女性。在每个药物组中，10名妇女将被随机分配到两个队列中的一个。妇女 队列1中的受试者将前往诊所，并提供母乳和血液样本，将其分成两等份。 将在严格的研究采集条件下处理和储存等分试样1。将处理等分试样2 并在模拟的家庭收集条件下储存。在不同的条件下储存相同的样品， 允许将家庭采集与诊所采集的金标准进行比较。从队列1收集的数据 将与来自合作网络的现有PK数据相结合，以构建群体PK模型。这些PK 模型将用于生成模型预测的浓度，并将其与家庭收集的浓度进行比较。 队列2的浓度。将为队列2中的女性提供上门采集的说明和用品 母乳和干血斑样本将被运往加州大学圣地亚哥分校。在家集中- 将采集的样本与上述生成的PK模型的模型预测浓度进行比较。 通过成功验证家庭收集的方法，拟议的研究将改变药物研究 通过极大地扩大可以参与的妇女人数，最终导致母乳喂养， 有足够的哺乳期安全性数据的药物数量呈指数级增长。的 本R21提案中开发的方法将用于为一项大型前瞻性、机会性的多项试验提供信息。 该公司将与美国和欧洲的大型网络合作。