Investigating the potential role of multi-drug resistance protein (MRP) transporters in fetal to maternal glyburide efflux in the human placenta.
Glyburide, a drug used to treat gestational diabetes has previously been shown not to be measurable in fetal blood, and to be transferred from the fetal to the maternal circulation against a concentration gradient. The objective of the study is to determine whether indomethacin, an inhibitor of the multi-drug resistance family (MRP) of transporters is involved in the active efflux of glyburide from the fetus to the mother. Using the dually perfused human placental cotyledon model, 12 perfusions were performed of both glyburide and indomethacin concomitantly. The rate of transfer of glyburide in the presence of inhibitor was not different from the rate of transfer of glyburide in the absence of inhibitor. Furthermore, our study suggests that MRP1, 2 or 3 may be only minimally involved in the transport of glyburide across the human placenta. These results pose other ABC transporters, such as likely candidates for the placental transfer of glyburide.
Department of Clinical Pharmacology, Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada.
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Gedeon
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Anger
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Lubetsky
M Piquette
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Miller
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Koren
D000328:Adult; D016640:Diabetes, Gestational / Q000188:drug therapy; D005260:Female; D005905:Glyburide / Q000493:pharmacokinetics* / Q000494:pharmacology / Q000627:therapeutic use; D006801:Humans; D007004:Hypoglycemic Agents / Q000493:pharmacokinetics* / Q000494:pharmacology / Q000627:therapeutic use; D007213:Indomethacin / Q000493:pharmacokinetics* / Q000494:pharmacology; D008297:Male; D008431:Maternal-Fetal Exchange; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000378:metabolism*; D010920:Placenta / Q000378:metabolism*; D011247:Pregnancy
D005905:Glyburide; D007004:Hypoglycemic Agents; D007213:Indomethacin; D027425:ATP-Binding Cassette, Sub-Family C Proteins