Factors Influencing Placental Transfer of Lopinavir: Binding, Uptake and Efflux

FACTORS INFLUENCING PLACENTAL TRANSFER OF LOPINAVIR: BINDING, UPTAKE AND EFFLUX By Abhishek Gulati, B. Pharm., M. Pharm. A Thesis submitted in partial fulfillment of the requirements for the degree of Master of Science at Virginia Commonwealth University. Virginia Commonwealth University, 2009 Major Director: Phillip M. Gerk, Pharm.D., Ph.D. Assistant Professor, Department of Pharmaceutics HIV protease inhibitors are an important component of Highly Active Antiretroviral Therapy used to treat HIV infected pregnant women. They have a low placental transfer and are highly plasma protein bound. The purpose of this thesis was to characterize the factors limiting placental passage and fetal exposure to lopinavir. These factors include lopinavir plasma protein binding and uptake, cellular binding, and efflux of lopinavir in the placental trophoblast cells. First, we determined the unbound fraction of lopinavir in cord blood and characterized the binding of lopinavir to α1-acid glycoprotein (AAG) and human serum