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Functional Role of P-Glycoprotein and Binding Protein Effect on the Placental Transfer of Lopinavir/Ritonavir in the Ex Vivo Human Perfusion Model
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 concentrati...
Autores principales: | , , , , , , |
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Formato: | Texto |
Lenguaje: | English |
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Hindawi Publishing Corporation
2009
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2778444/ https://www.ncbi.nlm.nih.gov/pubmed/19960055 http://dx.doi.org/10.1155/2009/726593 |
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author | Ceccaldi, Pierre-Francois Gavard, Laurent Mandelbrot, Laurent Rey, Elisabeth Farinotti, Robert Treluyer, Jean-Marc Gil, Sophie |
author_facet | Ceccaldi, Pierre-Francois Gavard, Laurent Mandelbrot, Laurent Rey, Elisabeth Farinotti, Robert Treluyer, Jean-Marc Gil, Sophie |
author_sort | Ceccaldi, Pierre-Francois |
collection | PubMed |
description | 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 [−0.156, −0.002], P = .046) 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. |
format | Text |
id | pubmed-2778444 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2009 |
publisher | Hindawi Publishing Corporation |
record_format | MEDLINE/PubMed |
spelling | pubmed-27784442009-12-03 Functional Role of P-Glycoprotein and Binding Protein Effect on the Placental Transfer of Lopinavir/Ritonavir in the Ex Vivo Human Perfusion Model Ceccaldi, Pierre-Francois Gavard, Laurent Mandelbrot, Laurent Rey, Elisabeth Farinotti, Robert Treluyer, Jean-Marc Gil, Sophie Obstet Gynecol Int Research Article 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 [−0.156, −0.002], P = .046) 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. Hindawi Publishing Corporation 2009 2009-05-18 /pmc/articles/PMC2778444/ /pubmed/19960055 http://dx.doi.org/10.1155/2009/726593 Text en Copyright © 2009 Pierre-Francois Ceccaldi et al. https://creativecommons.org/licenses/by/3.0/ 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. |
spellingShingle | Research Article Ceccaldi, Pierre-Francois Gavard, Laurent Mandelbrot, Laurent Rey, Elisabeth Farinotti, Robert Treluyer, Jean-Marc Gil, Sophie Functional Role of P-Glycoprotein and Binding Protein Effect on the Placental Transfer of Lopinavir/Ritonavir in the Ex Vivo Human Perfusion Model |
title | Functional Role of P-Glycoprotein and Binding Protein Effect on the Placental Transfer of Lopinavir/Ritonavir in the Ex Vivo Human Perfusion Model |
title_full | Functional Role of P-Glycoprotein and Binding Protein Effect on the Placental Transfer of Lopinavir/Ritonavir in the Ex Vivo Human Perfusion Model |
title_fullStr | Functional Role of P-Glycoprotein and Binding Protein Effect on the Placental Transfer of Lopinavir/Ritonavir in the Ex Vivo Human Perfusion Model |
title_full_unstemmed | Functional Role of P-Glycoprotein and Binding Protein Effect on the Placental Transfer of Lopinavir/Ritonavir in the Ex Vivo Human Perfusion Model |
title_short | Functional Role of P-Glycoprotein and Binding Protein Effect on the Placental Transfer of Lopinavir/Ritonavir in the Ex Vivo Human Perfusion Model |
title_sort | functional role of p-glycoprotein and binding protein effect on the placental transfer of lopinavir/ritonavir in the ex vivo human perfusion model |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2778444/ https://www.ncbi.nlm.nih.gov/pubmed/19960055 http://dx.doi.org/10.1155/2009/726593 |
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