Role of human placental apical membrane transporters in the efflux of glyburide, rosiglitazone, and metformin
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Objective Substrates of placental efflux transporters could compete for a single transporter, which could result in an increase in the transfer of each substrate to the fetal circulation. Our aim was to determine the role of placental transporters in the biodisposition of oral hypoglycemic drugs that could be used as monotherapy or in combination therapy for gestational diabetes. Study design Inside-out brush border membrane vesicles from term placentas were used to determine the efflux of glyburide, rosiglitazone, and metformin by P-glycoprotein, breast cancer resistance protein, and multidrug resistance protein. Results Glyburide was transported by multidrug resistance protein (43 +/- 4%); breast cancer resistance protein (25 +/- 5%); and P-glycoprotein (9 +/- 5%). Rosiglitazone was transported predominantly by P-glycoprotein (71 +/- 26%). Metformin was transported by P-glycoprotein (58 +/- 20%) and breast cancer resistance protein (25 +/- 14%). Conclusion Multiple placental transporters contribute to efflux of glyburide, rosiglitazone, and metformin. Administration of drug combinations could lead to their competition for efflux transporters.
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The actions of PPARγ in the brain of murine models of AD have been controversial, largely due to poor penetrance of its agonists into the brain and active P-glycoprotein-mediated efflux mechanisms.
“The actions of PPARγ in the brain of murine models of AD have been controversial, largely due to the poor penetrance of its agonists into the brain and active P-glycoprotein-mediated efflux mechanisms (Maeshiba et al., 1997; Hemauer et al., 2010).”
From Mechanisms Underlying the Rapid Peroxisome Proliferator-Activated Receptor-γ-Mediated Amyloid Clearance and Reversal of Cognitive Deficits in a Murine Model of Alzheimer's Disease (2012) · cites this paper as Hemauer et al., 2010
The COMMENT section (page not available) says P-glycoprotein transports rosiglitazone from brain to blood, supporting an efflux mechanism for that agonist. The paper does not establish poor brain penetration of PPARγ agonists generally or link that mechanism to controversy about PPARγ actions in murine Alzheimer’s disease models. (LLM, conf=0.86)
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Excretion of Drugs and Their Metabolites into the Bile
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- Authors
- Hemauer, S. J., Patrikeeva, S. L., Nanovskaya, T. N., Hankins, G. D. V., & Ahmed, M. S.
- Affiliations
- The University of Texas Medical Branch at Galveston (US)
- Venue
- American Journal of Obstetrics and Gynecology
- Publisher
- Elsevier BV
- Published
- 2010-04
- Volume
- 202
- Issue
- 4
- Pages
- 383.e1-383.e7
- ISSN
- 0002-9378 (ISSN-L)
- PMC
- PMC2848180
- OpenAlex
- W2022957471
- Cited by
- 103
- References
- 37
- Citations by year
- 2026: 2 · 2025: 2 · 2024: 2 · 2023: 6 · 2022: 5 · 2021: 6 · 2020: 7 · 2019: 4 · 2018: 7 · 2017: 7 · 2016: 11 · 2015: 6 · 2014: 8 · 2013: 9 · 2012: 6
- FWCI
- 4.47
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- American Journal of Obstetrics and Gynecology (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- UTMB Department of Obstetrics and Gynecology
- 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
- glibenclamide, rosiglitazone, metformin, P-glycoprotein, ABCG2, multidrug resistance protein, oral antidiabetic drugs, gestational diabetes mellitus, prenatal drug exposure, maternal-fetal drug transfer
- MeSH terms
- Rosiglitazone, Adenosine Triphosphate, Biological Transport, Carbon Radioisotopes, Carrier Proteins, Drug Interactions, Female, Glyburide, Humans, Hypoglycemic Agents, Maternal-Fetal Exchange, Metformin, Microvilli, Placenta, Pregnancy, Tritium, Diabetes, Gestational, Cell Polarity, Thiazolidinediones
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