PHARMACOKINETIC PROPERTIES OF ANITRETROVIRAL DRUGS DURING PREGNANCY

本子项目是利用由NIH/NCRR资助的中心赠款提供的资源的众多研究子项目之一。子项目和研究者（PI）可能已经从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。列出的机构是中心的，不一定是研究者的机构。研究抗逆转录病毒药物在孕妇中的药代动力学的临床试验是有限的。为孕妇制定适当的给药方案对母亲和胎儿的健康都至关重要。过量可能导致产妇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，产生耐药突变的风险增加，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。除了药物因素外，孕妇可能特别容易感染艾滋病毒。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，母亲的免疫系统至少部分被抑制，糖皮质激素的升高（与诱导肝脏代谢有关）是这种反应的一个组成部分。本研究旨在描述目前用于艾滋病毒感染孕妇临床护理的抗逆转录病毒药物在怀孕期间的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怀孕期间产生足够的药物暴露：a)来自非怀孕成年人的历史数据；b)研究队列中同样的女性在产后时期。在本方案中选择的研究药物/组合是在PACTG数据库中最常用的缺乏妊娠期间药代动力学数据的药物/组合。

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.