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: 8166661
• 负责人: William Thomas Shearer
• 金额: $ 1.48万
• 依托单位: BAYLOR COLLEGE OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-12-01 至 2010-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8166661
• 关键词: Adult; Adverse event; Anti-Retroviral Agents; Clinical Trials; Cohort Studies; Computer Retrieval of Information on Scientific Projects Database; 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; Institution; Lead; Left; Metabolism; Mothers; Overdose; Perinatal; Pharmaceutical Preparations; Physiological; Plasma; Postpartum Period; Pregnancy; Pregnant Women; Property; Regimen; Research; Research Personnel; Resources; Risk; Source; Therapeutic; Time; Tissues; Toxic effect; Umbilical Cord Blood; United States National Institutes of Health; Urine; Viral; Woman; clinical care; 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. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. 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. Primary Objective: To describe the PK parameters during pregnancy 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 Objectives: 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.

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 研究抗逆转录病毒药物在孕妇体内的药代动力学的临床试验有限。为孕妇制定适当的剂量方案对母亲和胎儿的健康都至关重要。过量服药可能会导致母体不良事件和增加胎儿毒性的风险。剂量不足可能导致病毒学控制不足，增加发生抗药性突变的风险，并导致围产期艾滋病毒传播率更高。怀孕期间新陈代谢增加和免疫反应抑制都会使母亲面临病毒突破和疾病进展的风险。与药物因素无关，孕妇可能处于艾滋病毒疾病进展的特别风险中。怀孕会在抗原性不同的组织之间产生暂时的生理和免疫平衡。为了适应胎儿，母亲的免疫系统至少部分受到抑制，糖皮质激素(涉及诱导肝脏代谢)的升高是这种反应的一个组成部分。 主要目的：描述目前用于妊娠HIV感染妇女临床护理的选定抗逆转录病毒药物在妊娠期的PK参数，并确定这些抗逆转录病毒药物的治疗剂量方案是否在妊娠期产生足够的药物暴露，与a)来自非怀孕成年人的历史数据；以及b)研究队列中的相同妇女在产后时期。 第二目的：比较分娩时脐带血和母体血浆中抗逆转录病毒药物的浓度。 通过测定尿液中6B-羟基皮质醇与皮质醇的比值，间接评价细胞色素P450 3A4的诱导作用。