PHARMACOKINETIC PROPERTIES OF ANITRETROVIRAL DRUGS DURING PREGNANCY

该子项目是利用NIH/NCRR资助的中心赠款提供的资源的许多研究子项目之一。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。所列机构为中心，不一定是研究者所在机构。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。 本研究旨在描述目前用于妊娠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，与以下数据相比：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。本方案中选择用于研究的药物/联合用药是PACTG数据库中最常用的药物/联合用药，该数据库缺乏妊娠期间的药代动力学数据。

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 homeostasis 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. The present study aims 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. The drugs/combinations selected for study in this protocol were among those most commonly used in the PACTG database that lacked pharmacokinetic data during pregnancy.