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.

项目概要 母乳喂养是推荐的婴儿主要营养来源，并且与认知能力有关 以及对发育中的儿童的其他健康益处。据估计 50-80% 的女性服用处方药 母乳喂养期间，但只有 2% 的药物有足够的数据来评估其在母乳喂养时的安全性 哺乳期。这代表了知识上的重大差距，导致许多女性要么避免必要的 药物治疗或停止母乳喂养。确定药物进入体内程度的主要障碍 母乳正在收集足够的母乳和血液样本来量化药物浓度和计算 药物暴露的个体差异。由于多种原因，新妈妈们往往很难来 进行考察访问。为了生成急需的药物进入母乳的数据，需要使用其他方法 需要收集样本，以使更多的哺乳期妇女参与并产生足够的 大量数据可以就母乳喂养期间给定药物的安全性提出强有力的建议。 该提案将严格检验家庭采集母乳和血液样本的中心假设 将针对更传统的基于临床的药代动力学 (PK) 收集方法进行成功​​验证 研究。以现有加州大学圣地亚哥分校母乳研究生物库研究的基础设施为基础 以及加州大学圣地亚哥分校和犹他大学的高素质、多学科研究团队，我们将招募 20 名母乳喂养妇女已服用泼尼松、羟考酮、舍曲林或哌醋甲酯，以治疗 共有80名女性。在每个药物组中，10 名女性将被随机分配到两个队列之一。女性 第 1 组将向诊所提供母乳和血液样本，并将其分成两份。 等份 1 将在严格的研究采集条件下进行处理和储存。将处理等分 2 并储存在模拟家庭收集条件下。在不同条件下保存相同的样品会 允许将家庭收集与诊所收集的黄金标准进行比较。从队列 1 收集的数据 将与合作网络的现有 PK 数据相结合，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 第 2 组的浓度。将为第 2 组的女性提供家庭收集的说明和用品 母乳和干血斑样本将被运送到加州大学圣地亚哥分校。在家集中注意力- 收集的样品将与上面生成的 PK 模型的模型预测浓度进行比较。 通过成功验证家庭收藏方法，拟议的研究将改变药物研究 通过大幅增加参与母乳喂养的女性人数，最终导致 具有足够哺乳安全数据的药物数量呈指数增长。这 本 R21 提案中开发的方法将用于为多项大型前瞻性、机会主义试验提供信息 药物涉及众多治疗领域，并将涉及与美国和欧洲大型网络的合作。