DRUG TRANSPORT/METABOLISM 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。 在这些脆弱人群中，药物是在没有必要临床数据的情况下给予孕妇的，因此也是给胎儿的。 为了确定妊娠期间给药药物的正确剂量，重要的是要了解妊娠女性与男性或非妊娠女性相比，药物的药代动力学是否不同。 妊娠期给药的许多药物是P-糖蛋白（P-gp）或细胞色素P450 3A酶（CYP 3A 4/5）或两者的底物。 我们有证据表明，对于两种用于治疗感染的抗病毒药物，与产后相比，妊娠30周时的总体药物暴露量减少了3-6倍。 这两种抗病毒药物均由CYP 3A 4/5代谢，并由P-gp转运。 本研究旨在评价妊娠期间与产后相比，女性身体如何处理地高辛（P-gp的底物）和咪达唑仑（CYP 3A 4/5的底物）。 受试者将接受两次地高辛（0.25 mg）口服给药和两次咪达唑仑（2 mg）口服给药。 一个地高辛研究日和一个咪达唑仑研究日将发生在妊娠晚期，另一个地高辛研究日和咪达唑仑研究日将发生在产后。 将在所有研究日采集血液和尿液样本。 本研究将招募妊娠28周前的健康妊娠女性。

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. Drugs are administered to pregnant women, and therefore their fetuses without the necessary clinical data in these vulnerable populations. To determine the correct dose of a drug to administer during pregnancy, it is important to know if the pharmacokinetics of the drug are different in pregnant women when compared with men or non-pregnant women. Many drugs administered in pregnancy are substrates of P-glycoprotein (P-gp) or cytochrome P450 3A enzymes (CYP3A4/5) or both. We have evidence that for two of the antiviral drugs used to treat infections there is a 3-6 fold decrease in overall drug exposure at 30 weeks gestation as compared to postpartum. Both of these antiviral drugs are metabolized by CYP3A4/5 and transported by P-gp. This study is designed to evaluate how a woman's body handles digoxin (a substrate for P-gp) and midazolam (a substrate for CYP3A4/5) during pregnancy as compared to postpartum. Subjects will receive two oral doses of digoxin (0.25 mg) and two oral doses of midazolam (2 mg). One digoxin study day and one midazolam study day will occur during the 3rd trimester of pregnancy and the other digoxin study day and midazolam study day will occur postpartum. Blood and urine samples will be collected throughout all study days. Healthy pregnant women prior to 28 weeks gestation will be recruited for this study.