Grant: Project Grant

Many diseases require women to be on drug therapy during pregnancy, however there is little information on drug levels in mother and unborn baby. Several transporters are found in high amounts in the placenta and prevent the transfer of drugs from mother to fetus. The total amount of transporter in placenta influences the amount of drug that unborn babies get exposed to and resulting health problems. Studies in our laboratory in animal models of infection and inflammation showed decreased levels of transporters in placenta and increased amounts of drug in the fetus. Decreased amounts of transporters are also seen in placenta from women with viral and bacterial infections and our recent studies also see decreased transporters in placenta of women with preeclampsia. Many sudden or chronic diseases such as preeclampsia, lupus and arthritis are associated with inflammation. Therefore changes in placental transporters due to these diseases likely contribute to increased fetal drug exposure. The effect of disease, the underlying causes and the overall effect of these changes on the fetus remain unknown. Hypothesis: Altered levels and activity of transporters due to disease will influence fetal drug exposure. Research Strategy: We will examine the effect of preeclampsia and common inflammatory diseases on transporters in human placenta, examine what disease factors are responsible and the process by which this happens. Using experimental animal models we will then examine the impact of changes in transporter abundance and maternal disease on the amount of drug that mothers and their unborn babies are exposed to. Application: Diseases which occur in many pregnant women can alter levels of drug transporters which can affect the amount of drug that gets across placenta. The results from this study will help us to estimate how much drug gets to the unborn baby and will help in selecting drugs and doses for these women.