PACTG P1026S (VERSION 20), PHARMACOKINETIC PROPERTIES OF ANTIRETROVIRAL DRUG

PACTG P1026S（版本 20），抗逆转录病毒药物的药代动力学特性

• 批准号: 8356662
• 负责人: William Thomas Shearer
• 金额: $ 4.13万
• 依托单位: BAYLOR COLLEGE OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-12-01 至 2011-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8356662
• 关键词: Adult; Adverse event; Anti-Retroviral Agents; Clinical Research; Clinical Trials; Cohort Studies; Cytochrome P450 3A4; Data; Development; Disease; Disease Progression; Dose; Drug Exposure; Drug Kinetics; Drug resistance; Fetus; Funding; Glucocorticoids; Grant; HIV; Health; Hepatic; Hydrocortisone; Immune system; Immunologics; Lead; Left; Metabolism; Mothers; National Center for Research Resources; Overdose; Perinatal; Pharmaceutical Preparations; Physiological; Plasma; Postpartum Period; Pregnancy; Pregnant Women; Principal Investigator; Property; Regimen; Research; Research Infrastructure; Resources; Risk; Source; Therapeutic; Time; Tissues; Toxic effect; Umbilical Cord Blood; United States National Institutes of Health; Urine; Viral; Woman; clinical care; cost; fetal; pregnant; resistance mutation; response; transmission process

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. ABSTRACT HYPOTHESIS Clinical trials to study the pharmacokinetics of antiretroviral drugs in pregnant women are limited. The development of appropriate dosing regimens for the pregnant woman is critical to the health of both mother and fetus. Overdosing may lead to maternal adverse events and increased risk of fetal toxicity. Underdosing may lead to inadequate virologic control, increased risk of developing drug resistance mutations and a higher rate of perinatal HIV transmission. Both increased metabolism and suppressed immunologic response during pregnancy can leave the mother at risk for viral breakthrough and progression of disease. Independent of pharmacologic factors, pregnant women may be at particular risk for progression of their HIV disease. Pregnancy produces a temporary physiologic and immunologic homeostatis between tissues that are antigenically different. In order to accommodate the fetus, the maternal immune system is at least partially suppressed with an elevation of glucocorticoids (implicated in inducing hepatic metabolism) as one component of this response. SPECIFIC AIMS Primary Objective: To describe the PK parameters during pregnacy of selected antiretroviral drugs currently used in the clinical care of pregnant HIV-infected women, and to determine if therapeutic dosing regimens of these antiretroviral drugs produce adequate drug exposure during pregnancy compared to a) historical data from non-pregnant adults; and b) the same women in the study cohorts during the postpartum period. Secondary Obectives: To compare antiretroviral drug concentrations is plasma from cord blood with those in maternal plasma at the time of delivery. To indirectly assess the induction of cytochrome P450 3A4 by determining the ratio in urine of 6B-hydroxycortisol to cortisol.

该子项目是利用资源的众多研究子项目之一 由 NIH/NCRR 资助的中心拨款提供。子项目的主要支持 并且子项目的首席研究员可能是由其他来源提供的， 包括其他 NIH 来源。 子项目可能列出的总成本 代表子项目使用的中心基础设施的估计数量， NCRR 赠款不直接向子项目或子项目工作人员提供资金。 抽象的 假设 研究孕妇抗逆转录病毒药物药代动力学的临床试验有限。 为孕妇制定适当的给药方案对于母亲和胎儿的健康至关重要。 过量服用可能会导致母体不良事件并增加胎儿毒性的风险。 剂量不足可能导致病毒学控制不足、产生耐药性突变的风险增加以及围产期艾滋病毒传播率升高。 怀孕期间新陈代谢的增加和免疫反应的抑制都会使母亲面临病毒突破和疾病进展的风险。 与药理学因素无关，孕妇可能面临艾滋病毒疾病进展的特殊风险。 怀孕会在抗原不同的组织之间产生暂时的生理和免疫稳态。 为了适应胎儿，母体免疫系统至少部分受到抑制，糖皮质激素的升高（涉及诱导肝脏代谢）是这种反应的一个组成部分。 具体目标 主要目的：描述目前在 HIV 感染孕妇临床护理中使用的选定抗逆转录病毒药物在怀孕期间的 PK 参数，并确定与 a) 历史数据相比，这些抗逆转录病毒药物的治疗剂量方案是否在怀孕期间产生足够的药物暴露来自非怀孕的成年人； b) 产后期研究队列中的相同女性。 次要目标：比较脐带血血浆中的抗逆转录病毒药物浓度与分娩时母体血浆中的抗逆转录病毒药物浓度。 通过测定尿液中 6B-羟基皮质醇与皮质醇的比率来间接评估细胞色素 P450 3A4 的诱导作用。