Functional Role of P-Glycoprotein and Binding Protein Effect on the Placental Transfer of Lopinavir/Ritonavir in the Ex Vivo Human Perfusion Model
Open accessAbstract
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.
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Inhibition of P-glycoprotein increases transfer of the antiretroviral drugs lopinavir and retinavir to the fetal perfusate, confirming its role as an efflux transporter.
“In addition, the system is manipulable; for example, inhibition of G-glycoprotein increases transfer of the antiretroviral drugs lopinavir and retinavir to the fetal perfusate, confirming its role as an efflux transporter (100).”
From Placental Origins of Chronic Disease (2016) · cites this paper as [100]
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Placental Origins of Chronic Disease
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- Authors
- Ceccaldi, P.-F., Gavard, L., Mandelbrot, L., Rey, E., Farinotti, R., Treluyer, J.-M., & Gil, S.
- Affiliations
- Department of Obstetrics and Gynecology, Louis Mourier Hospital, AP-HP, Paris 7 University, 92701 Colombes, France
- Université Paris-Sud (FR)
- Hôpital Louis-Mourier (FR)
- Assistance Publique – Hôpitaux de Paris (FR)
- Department of Pediatric Pharmacology, Saint Vincent de Paul Hospital, AP-HP, Paris 5 University, 75014 Paris, France
- Corresponding author
- Gil, Sophie
- Venue
- Obstetrics and Gynecology International
- Publisher
- Wiley
- Published
- 2009
- Volume
- 2009
- Pages
- 1-6
- ISSN
- 1687-9589 (ISSN-L)
- 1687-9597
- PMC
- PMC2778444
- OpenAlex
- W1967395741
- Cited by
- 37
- References
- 24
- Citations by year
- 2026: 1 · 2024: 2 · 2022: 2 · 2021: 5 · 2020: 4 · 2019: 2 · 2018: 1 · 2017: 2 · 2016: 1 · 2015: 4 · 2014: 3 · 2013: 2 · 2012: 4
- FWCI
- 1.33
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Obstetrics and Gynecology International (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- Abbott Laboratories
- Topics
- Health Sciences › Medicine › Oncology › Drug Transport and Resistance Mechanisms
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Pregnancy and Medication Impact
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmacology › Pharmacogenetics and Drug Metabolism
- Keywords
- P-glycoprotein, MDR1, placental transfer, lopinavir, ritonavir, albumin-binding protein, cyclosporine, clearance index, antiretroviral therapy, prenatal exposure, drug efflux
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