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 怀孕期间的抑郁和焦虑影响了10%以上的妇女，6-8%的孕妇接受了 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 在育龄妇女中使用SSRI。然而，仍然有有限的信息来优化其 怀孕期间的治疗。舍曲林显示出很大的个体间变异性，尽管研究通常受到 小样本和不一致的观察。伴随怀孕的生理变化可以 改变药物药代动力学（例如，清除率），这可能会显着影响稳态浓度 药物，支持剂量调整的需要，以维持孕前药物暴露。我们 目的是量化舍曲林药代动力学暴露对孕产妇健康的影响， 产科/新生儿结局。妇女心理健康计划数据库前瞻性地包含 收集了超过2,500名患有神经精神疾病的人的数据， 在围产期和产后期间进行独特的访问。舍曲林和代谢物浓度沿着 产妇症状和产科/新生儿结局信息将通过以下方式进行分析 药代动力学/药效学建模，能够表征变化之间的关系 舍曲林暴露与母亲抑郁症状和妊娠期新生儿结局的关系， 产后该项目的结果将支持剂量策略的改进和循证医学 妊娠期间使用舍曲林的个性化治疗计划。药代动力学的应用- 指导给药将加强对疾病相关症状的预防，并改善孕产妇和 儿童健康。本课题为其他抗抑郁药和精神药物的研究提供了基础 怀孕期间使用的药物。