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...
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| Format: | Article |
| Language: | English |
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Wiley
2009-01-01
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| Series: | Obstetrics and Gynecology International |
| Online Access: | http://dx.doi.org/10.1155/2009/726593 |
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| author | Pierre-Francois Ceccaldi Laurent Gavard Laurent Mandelbrot Elisabeth Rey Robert Farinotti Jean-Marc Treluyer Sophie Gil |
| author_facet | Pierre-Francois Ceccaldi Laurent Gavard Laurent Mandelbrot Elisabeth Rey Robert Farinotti Jean-Marc Treluyer Sophie Gil |
| author_sort | Pierre-Francois Ceccaldi |
| collection | DOAJ |
| 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 | Article |
| id | doaj-art-59e830224d454df09e43b9aed49009ad |
| institution | Kabale University |
| issn | 1687-9589 1687-9597 |
| language | English |
| publishDate | 2009-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Obstetrics and Gynecology International |
| spelling | doaj-art-59e830224d454df09e43b9aed49009ad2025-02-03T01:32:56ZengWileyObstetrics and Gynecology International1687-95891687-95972009-01-01200910.1155/2009/726593726593Functional Role of P-Glycoprotein and Binding Protein Effect on the Placental Transfer of Lopinavir/Ritonavir in the Ex Vivo Human Perfusion ModelPierre-Francois Ceccaldi0Laurent Gavard1Laurent Mandelbrot2Elisabeth Rey3Robert Farinotti4Jean-Marc Treluyer5Sophie Gil6Department of Obstetrics and Gynecology, Louis Mourier Hospital, AP-HP, Paris 7 University, 92701 Colombes, FranceDepartment of Obstetrics and Gynecology, Louis Mourier Hospital, AP-HP, Paris 7 University, 92701 Colombes, FranceDepartment of Obstetrics and Gynecology, Louis Mourier Hospital, AP-HP, Paris 7 University, 92701 Colombes, FranceDepartment of Pediatric Pharmacology, Saint Vincent de Paul Hospital, AP-HP, Paris 5 University, 75014 Paris, FranceFaculty of Pharmacy, University Paris-Sud, EA2706, 92296 Châtenay-Malabry, FranceDepartment of Pediatric Pharmacology, Saint Vincent de Paul Hospital, AP-HP, Paris 5 University, 75014 Paris, FranceFaculty of Pharmacy, University Paris-Sud, EA2706, 92296 Châtenay-Malabry, FranceAims. 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.http://dx.doi.org/10.1155/2009/726593 |
| spellingShingle | Pierre-Francois Ceccaldi Laurent Gavard Laurent Mandelbrot Elisabeth Rey Robert Farinotti Jean-Marc Treluyer Sophie Gil Functional Role of P-Glycoprotein and Binding Protein Effect on the Placental Transfer of Lopinavir/Ritonavir in the Ex Vivo Human Perfusion Model Obstetrics and Gynecology International |
| 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 |
| url | http://dx.doi.org/10.1155/2009/726593 |
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