Pharmacokinetic/Pharmacodynamic model in pregnant women with depression to guide sertraline dosing

抑郁症孕妇的药代动力学/药效学模型指导舍曲林给药

• 批准号: 10685934
• 负责人: ANGELA K BIRNBAUM
• 金额: $ 18.92万
• 依托单位: UNIVERSITY OF MINNESOTA
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-08-18 至 2024-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10685934
• 关键词: 37 weeks gestation; Admission activity; Adverse effects; Affect; Antidepressive Agents; Anxiety; Apgar Score; Area; Beck depression inventory; Birth; Birth Weight; CYP2C19 gene; CYP2C9 gene; CYP2D6 gene; CYP3A4 gene; Caring; Characteristics; Clinical; Clinical Practice Guideline; Collaborations; Cytochrome P450; Data; Databases; Development; Discipline of obstetrics; Disease; Dose; Drug Exposure; Drug Kinetics; Enzymes; Equilibrium; Exposure to; Fetus; Fostering; Foundations; Gestational Age; Goals; Hamilton Rating Scale for Depression; Height; Hypoglycemia; Individual; Investigation; Knowledge; Length of Stay; Low Birth Weight Infant; Maternal Health; Maternal and Child Health; Measures; Mental Depression; Mental Health; Metabolism; Modeling; Neonatal; Neonatal Intensive Care Units; Oral; Outcome; Oxygen; Pharmaceutical Preparations; Physiological; Physiology; Population; Postpartum Depression; Postpartum Period; Pregnancy; Pregnant Women; Premature Birth; Research; Resources; Sample Size; Selective Serotonin Reuptake Inhibitor; Sertraline; Small for Gestational Age Infant; Symptoms; Time; Universities; Visit; Weight; Woman; adverse outcome; antidepressant effect; biobank; career development; depressive symptoms; disorder prevention; evidence base; improved; individualized medicine; inter-individual variation; neonatal outcome; neuropsychiatry; perinatal outcomes; perinatal period; personalized medicine; pharmacodynamic model; pharmacologic; pregnant; prepregnancy; prevent; primary outcome; programs; prospective; reproductive; response; treatment planning

Abstract Depression and anxiety during pregnancy affect over 10% of women with 6-8% of pregnant women receiving a prescription for a selective serotonin reuptake inhibitor (SSRI) antidepressant. Sertraline is the most commonly prescribed SSRI in women of reproductive years. However, there remains limited information for optimizing its treatment during pregnancy. Sertraline shows large inter-individual variability although studies generally suffer from small sample sizes and inconsistent observations. Physiological changes accompanying pregnancy can alter drug pharmacokinetics (e.g., clearance) which can significantly affect steady-state concentrations of medications, supporting the need for dose adjustments in order to maintain pre-pregnancy drug exposure. Our objective is to quantify the contribution of sertraline pharmacokinetic exposure to maternal health and obstetrical/neonatal outcomes. The Women’s Mental Health Program database contains prospectively collected data from more than 2,500 individuals with neuropsychiatric illnesses across more than 15,000 unique visits during the perinatal and postpartum periods. Sertraline and metabolite concentrations along with maternal symptoms and obstetrical/neonatal outcome information will be analyzed via pharmacokinetic/pharmacodynamic modeling enabling characterization of the relationships between changes in sertraline exposure with maternal symptoms of depression and neonatal outcomes during pregnancy and postpartum. Results from this project will support refinement of dosing strategies and evidence-based personalized treatment planning for the use of sertraline during pregnancy. The application of pharmacokinetic- guided dosing will result in enhanced prevention of disease-related symptoms and improved maternal and child health. This project will provide the foundation for investigation of other antidepressants and psychotropic medications used during pregnancy.

摘要 超过10%的妇女在怀孕期间受到抑郁和焦虑的影响，其中6%-8%的孕妇接受了 一种选择性5-羟色胺再摄取抑制剂(SSRI)抗抑郁药的处方。舍曲林是最常见的 育龄妇女的SSRI处方。然而，优化ITS的信息仍然有限 怀孕期间的治疗。舍曲林表现出很大的个体间变异性，尽管研究通常会 来自小样本量和不一致的观察。伴随着怀孕的生理变化可能 改变药物的药代动力学(例如，清除)，这会显著影响药物的稳态浓度 药物，支持需要调整剂量，以维持孕前药物暴露。我们的 目的是量化舍曲林药代动力学暴露对孕产妇健康和 产科/新生儿结局。妇女心理健康计划数据库预期包含 收集了超过15,000名超过2,500名神经精神疾病患者的数据 在围产期和产后期进行独特的探视。舍曲林和代谢物浓度以及 产妇症状和产科/新生儿结局信息将通过 药代动力学/药效学建模能够表征变化之间的关系 孕期母体抑郁症状和新生儿结局与舍曲林暴露的关系 产后。该项目的结果将支持剂量策略的改进和基于证据的 孕期使用舍曲林的个体化治疗计划。药代动力学的应用- 引导剂量将导致加强对疾病相关症状的预防，并改善孕产妇和 儿童健康。该项目将为其他抗抑郁药物和精神药物的研究提供基础 怀孕期间使用的药物。