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

基本信息

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
项目类别：
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

项目摘要

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.

抽象的怀孕期间的抑郁和焦虑影响超过 10% 的女性，其中 6-8% 的孕妇接受孕期抑郁和焦虑治疗。选择性血清素再摄取抑制剂 (SSRI) 抗抑郁药是最常见的处方。育龄妇女服用 SSRI 然而，优化其效果的信息仍然有限。怀孕期间的治疗显示，尽管个体间差异较大，但舍曲林的研究通常会受到影响。来自小样本量和不一致的观察结果可能会导致怀孕期间的生理变化。改变药物药代动力学（例如清除率），这可以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。目的是量化舍曲林药代动力学暴露对孕产妇健康的贡献妇女心理健康计划数据库包含前瞻性的产科/新生儿结果。收集了超过 15,000 名患有神经精神疾病的 2,500 多名患者的数据围产期和产后期间的独特访视以及舍曲林和代谢物浓度。将通过以下方式分析孕产妇症状和产科/新生儿结果信息药代动力学/药效关系建模能够表征之间的变化怀孕期间因舍曲林暴露而出现抑郁症母亲症状和新生儿结局的情况该项目的结果将支持剂量策略的完善和基于证据的。妊娠期间使用舍曲林的个性化治疗计划。指导用药将加强对疾病相关症状的预防，并改善孕产妇和该项目将为其他抗抑郁药和精神药物的研究奠定基础。怀孕期间使用的药物。