Grant: Project Grant

Lupus is an immune disease that most commonly occurs in women of childbearing age. During pregnancy, women with lupus often get worse or frequently develop complications such as preeclampsia, so they must take drugs to control their disease. Despite requiring drug therapy during pregnancy, there is little information on how lupus affects drug levels in mother and unborn baby. PGP and BCRP are transport proteins found in placenta that block and prevent the movement of drugs from mother to fetus. Our initial studies found that amounts of PGP are decreased in placenta of women with lupus and BCRP is decreased in preeclampsia. Many drugs used to treat lupus and its complications are transported by PGP and BCRP, therefore the reduced amounts of transporters found in placenta could cause an increase in drug exposure to the unborn child. The effect of disease, the underlying causes and the overall effect of these changes on the fetus remain unknown. We believe that changes in the amount of transporters in placenta due to disease may alter fetal drug exposure and increase the potential for negative outcomes. Therefore, using human placenta tissues and cells, we propose to look at the effect of lupus and its complications on transporters in placenta and examine the causes of these changes. Next, using experimental animal models, we will examine the impact of lupus on drug levels in mothers, how much drug gets to the fetus and pregnancy outcomes. Real world information on drug use and pregnancy outcomes will be generated from Canadian medical databases and used to both guide these studies and evaluate clinical importance. Diseases which occur in pregnant women can alter levels of drug transporters which can affect the amount of drug that gets across placenta. Information that we get from these studies will help us to estimate how much drug gets to the unborn baby and will help in selecting drugs and doses for these women.