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: 7950597
• 负责人: William Thomas Shearer
• 金额: $ 11.63万
• 依托单位: BAYLOR COLLEGE OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-12-01 至 2009-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7950597
• 关键词: Adult; Adverse event; Anti-Retroviral Agents; Clinical Research; 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; Research; Research Personnel; Resources; Risk; Source; Therapeutic; Time; Tissues; Toxic effect; Treatment Protocols; 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 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.

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 研究抗逆转录病毒药物在孕妇体内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母亲和胎儿的健康至关重要。 过量给药可能导致母体不良事件和胎儿毒性风险增加。 剂量不足可能导致病毒学控制不足，增加产生耐药性突变的风险，以及提高围产期艾滋病毒传播率。 怀孕期间代谢增加和免疫反应抑制都可能使母亲面临病毒突破和疾病进展的风险。 独立于药理学因素，孕妇可能处于艾滋病毒疾病进展的特殊风险中。 妊娠在抗原性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，糖皮质激素升高（涉及诱导肝脏代谢）作为这种反应的一个组成部分。 主要目的：描述目前用于妊娠HIV感染女性临床护理的选定抗逆转录病毒药物在妊娠期间的PK参数，并确定这些抗逆转录病毒药物的治疗性给药方案是否在妊娠期间产生足够的药物暴露，与a）非妊娠成人的历史数据;和B）研究队列中相同女性在产后期间相比。 次要目的：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6 B-羟基皮质醇与皮质醇的比值，间接评估细胞色素P450 3A 4的诱导作用。