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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| http://dx.doi.org/10.1016/j.ajog.2010.01.035 | DOI Listing |
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