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.
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