A STUDY OF THE PHARMACOLOGY OF 17-HYDROXYPROGESTERONE CAPROATE IN PREGNANCY

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。子项目及 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的研究机构。 最近完成的由国家儿童健康和人类发展研究所（NICHD）赞助的母胎医学单位（MFMU）网络的试验表明，肌内注射17-α-羟孕酮己酸酯（17-OHPC）大大降低了早产高危妇女的早产率，因为以前有自发性早产。没有其他预防早产的策略或治疗方法被证明是有效的。因此，美国妇产科医师学会谨慎地支持这种治疗，但指出需要更多关于这种疗法和替代疗法的信息。虽然有大量的证据表明这种治疗的安全性，但对这种药物的药理学几乎一无所知，特别是在怀孕期间。本研究的目的是确定17-羟孕酮己酸酯在妊娠期的药理学。本方案将重点关注药代动力学和胎盘转运，并提供17-OHPC药物流行病学的初步数据。本研究的主要研究问题是：IM注射250 mg 17-OHPC后，17-OHPC的药代动力学（以浓度-时间曲线下面积表示）在妊娠中期和妊娠晚期之间是否存在差异？对于研究的两个部分，我们将在注射17-OHPC前和注射后1周内每天采集血样（共8份样本），合格受试者可选择第三部分。此外，将在每周一次研究药物注射前和给药时采集血样。大约60名受试者（年龄18-45岁）将在产科胎儿药理学研究单位（OPRU）网络的一个研究中心招募，其中15名在匹兹堡大学医学中心的马吉妇女医院。研究治疗将持续至分娩。本多中心研究的总持续时间为2-3年。

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. The recently completed trial by the National Institute of Child Health and Human Development (NICHD)-sponsored Maternal-Fetal Medicine Units (MFMU) Network has demonstrated that intramuscular 17-alpha-hydroxyprogesterone caproate (17-OHPC) substantially reduces the rate of preterm birth in women at high risk for preterm delivery because of a prior spontaneous preterm birth. No other strategy or treatment for prevention of preterm birth has proven to be effective. Consequently, the American College of Obstetricians and Gynecologists has cautiously supported this treatment but points out that much more information about this therapy and alternative therapies is required. Although a large body of evidence exists about the safety of this treatment, almost nothing is known about the pharmacology of this agent, especially in pregnancy. The purpose of this study is to define the pharmacology of 17-hydroxyprogesterone caproate in pregnancy. This protocol will focus on pharmacokinetics and placental transport and provide preliminary data on the pharmacoepidemiology of 17-OHPC. The primary research question of this study is: Do the pharmacokinetics of 17-OHPC as represented by area under the concentration vs.time curve after IM injection of 250 mg 17-OHPC differ between the second and third trimesters of pregnancy? We will obtain blood samples prior to and daily for one week after injection of 17-OHPC (8 samples total) for each of two parts of the study, with an optional third part for eligible subjects. Additionally, blood samples will be collected prior to each weekly injection of the study drug and at time of delivery. Approximately 60 subjects (ages 18-45) will be accrued at one of the Obstetrical Fetal Pharmacology Research Units (OPRU) Network sites, with 15 at Magee-Womens Hospital of the University of Pittsburgh Medical Center. Study treatment will be administered until delivery. The total duration of this multi-center study is 2-3 years.