Reduced Maternal and Fetal Lopinavir Exposure in a Rat Model of Gestational Diabetes by LC-MS/MS

摘要

Gestational diabetes mellitus (GDM) decreases the plasma protein binding of lopinavir. GDM increases expression of hepatic Mdr1 and Cyp3a2 which results in decreased maternal lopinavir exposure. Consequently, there is a decrease in fetal lopinavir exposure. GDM increases placental Mdr1 which further limits mother-to-fetus transport (possibly counteracting the increased transfer expected to occur across this organ with decreased protein binding). This study advances our understanding of experimental GDM's impact on lopinavir disposition and provides preclinical support for an as yet unreported drug-disease (lopinavir-GDM) interaction.