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Obstetrics and Gynecology International
Volume 2009, Article ID 726593, 6 pages
http://dx.doi.org/10.1155/2009/726593
Research Article

Functional Role of P-Glycoprotein and Binding Protein Effect on the Placental Transfer of Lopinavir/Ritonavir in the Ex Vivo Human Perfusion Model

1Department of Obstetrics and Gynecology, Louis Mourier Hospital, AP-HP, Paris 7 University, 92701 Colombes, France
2Faculty of Pharmacy, University Paris-Sud, EA2706, 92296 Châtenay-Malabry, France
3Department of Pediatric Pharmacology, Saint Vincent de Paul Hospital, AP-HP, Paris 5 University, 75014 Paris, France
4Department of Pharmacy, Pitié-Salpétrière Hospital, AP-HP, 75013 Paris, France

Received 17 September 2008; Accepted 2 February 2009

Academic Editor: Michael G. Ross

Copyright © 2009 Pierre-Francois Ceccaldi et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Aims. To study the influence of P-glycoprotein (P-glycoprotein, ABCB1, MDR1) function on placental transfer of lopinavir with ritonavir at different albumin concentrations. Methods. Cotyledons were perfused with lopinavir, ritonavir, and the internal control antipyrin, at various albumin concentrations (10, 30, 40 g/L). After the control phase of each experiment, the P-glycoprotein inhibitor ciclosporin A was added at middle perfusion (45 minutes). Fetal Transfer Rate (FTR) and Clearance Index (CLI) were compared between the 2 phases. Results. In the control phase, the clearance index of lopinavir decreased from 0.401 0.058 to 0.007 0.027, as albumin concentrations increased from 10 g/L to higher concentrations (30, 40 g/L). When adding ciclosporin A at physiological albumin concentrations, the clearance index of lopinavir increased significantly 10.3 fold (95% of CI difference [ , ], ) and became positive for ritonavir. Conclusions. Even at high albumin concentrations, inhibition of placental P-glycoprotein increased placental transfer of lopinavir, suggesting that this efflux pump actively reduces placental transfer of the drug. This mechanism may play a role in fetal exposure to maternal antiretroviral therapy.