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Functional Role of P-Glycoprotein and Binding Protein Effect on the Placental Transfer of LopinavirRitonavir in the Ex Vivo Human Perfusion Model
Joint Authors
Gil, Sophie
Mandelbrot, Laurent
Gavard, Laurent
Rey, Elisabeth
Ceccaldi, Pierre-Francois
Treluyer, Jean-Marc
Farinotti, Robert
Source
Obstetrics and Gynecology International
Issue
Vol. 2009, Issue 2009 (31 Dec. 2009), pp.1-6, 6 p.
Publisher
Hindawi Publishing Corporation
Publication Date
2009-05-18
Country of Publication
Egypt
No. of Pages
6
Main Subjects
Abstract EN
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.
American Psychological Association (APA)
Ceccaldi, Pierre-Francois& Gavard, Laurent& Mandelbrot, Laurent& Rey, Elisabeth& Farinotti, Robert& Treluyer, Jean-Marc…[et al.]. 2009. Functional Role of P-Glycoprotein and Binding Protein Effect on the Placental Transfer of LopinavirRitonavir in the Ex Vivo Human Perfusion Model. Obstetrics and Gynecology International،Vol. 2009, no. 2009, pp.1-6.
https://search.emarefa.net/detail/BIM-493772
Modern Language Association (MLA)
Ceccaldi, Pierre-Francois…[et al.]. Functional Role of P-Glycoprotein and Binding Protein Effect on the Placental Transfer of LopinavirRitonavir in the Ex Vivo Human Perfusion Model. Obstetrics and Gynecology International No. 2009 (2009), pp.1-6.
https://search.emarefa.net/detail/BIM-493772
American Medical Association (AMA)
Ceccaldi, Pierre-Francois& Gavard, Laurent& Mandelbrot, Laurent& Rey, Elisabeth& Farinotti, Robert& Treluyer, Jean-Marc…[et al.]. Functional Role of P-Glycoprotein and Binding Protein Effect on the Placental Transfer of LopinavirRitonavir in the Ex Vivo Human Perfusion Model. Obstetrics and Gynecology International. 2009. Vol. 2009, no. 2009, pp.1-6.
https://search.emarefa.net/detail/BIM-493772
Data Type
Journal Articles
Language
English
Notes
Includes bibliographical references
Record ID
BIM-493772