OBJECTIVES: The distribution of drugs to the maternal-fetal interface is influenced by the expression of various efflux transporters. Among these transporters, P-glycoprotein (P-gp) is responsible for the efflux of a great number of drugs such as protease inhibitors of the human immunodeficiency virus, thus reducing the chemical exposure of the fetus. STUDY DESIGN: The effects of saquinavir and nelfinavir were evaluated on human trophoblast functions and integrity by investigating their effect on human chorionic gonadotropin (hCG) secretion and on P-gp expression and functionality. RESULTS: Nelfinavir significantly reduced hCG secretion by 30% after a 48-h treatment but it had no effect on syncytia formation. Saquinavir had no effect on hCG secretion but significantly increased both expression (to a 2-fold extent) and functionality (by 17.9%) of P-gp, whereas nelfinavir only increased functionality (by 23.1%) with a dissociation of P-gp from caveolin-1. CONCLUSION: These results suggest that the effects of saquinavir and nelfinavir differ on trophoblast functions. Copyright 2010 Elsevier Ireland Ltd. All rights reserved.
OBJECTIVES: The distribution of drugs to the maternal-fetal interface is influenced by the expression of various efflux transporters. Among these transporters, P-glycoprotein (P-gp) is responsible for the efflux of a great number of drugs such as protease inhibitors of the human immunodeficiency virus, thus reducing the chemical exposure of the fetus. STUDY DESIGN: The effects of saquinavir and nelfinavir were evaluated on human trophoblast functions and integrity by investigating their effect on human chorionic gonadotropin (hCG) secretion and on P-gp expression and functionality. RESULTS:Nelfinavir significantly reduced hCG secretion by 30% after a 48-h treatment but it had no effect on syncytia formation. Saquinavir had no effect on hCG secretion but significantly increased both expression (to a 2-fold extent) and functionality (by 17.9%) of P-gp, whereas nelfinavir only increased functionality (by 23.1%) with a dissociation of P-gp from caveolin-1. CONCLUSION: These results suggest that the effects of saquinavir and nelfinavir differ on trophoblast functions. Copyright 2010 Elsevier Ireland Ltd. All rights reserved.
Authors: Anand A Joshi; Soniya S Vaidya; Marie V St-Pierre; Andrei M Mikheev; Kelly E Desino; Abner N Nyandege; Kenneth L Audus; Jashvant D Unadkat; Phillip M Gerk Journal: Pharm Res Date: 2016-09-19 Impact factor: 4.200