Multidrug Resistant Transporters of the Placenta

Some P-gp inhibitors have been tested in clinical trials (e.g., GF120918, PSC 833) [88, 89], Shortly before birth, it is often desirable to expose the fetus to anti-HIV medications to prevent HIV transmission from the mother to the fetus during delivery. Preperfusion with P-gp inhibitors increased fetal penetration of the protease inhibitor saquinavir in in vitro placental models, and it has been hypothesized that P-gp may be responsible for limiting fetal exposure to HIV protease inhibitors, methadone, anthracyclines, and taxanes [90-93], 

It needs to be mentioned here that there remains some controversy over the placental expression of P-gp as a function of gestational age. An immunohis-tochemical study done by Macfarland et al. showed that P-gp was localized to the microvillous border of trophoblasts in first trimester placenta, but not in term placenta [85], Subsequent studies refuted this to show that MDR1 mRNA is present throughout pregnancy [94], More recently, enzyme-linked immunosorbent assay (ELISA) performed in syncytial microvillous membrane showed that P-gp protein expression in early gestational age placenta is about 

More information about the placental regulation of MDR1 will provide more options to choose from, when the intention is to modify its placental expression levels to either treat or protect the ferns. The various regulatory mechanisms of 

P-gp outlined above are potential pathways that can be exploited to improve or prevent the transplacental passage of drugs. It should be noted that most of these pathways involve a complex interplay of several factors that may vary in a cell- or tissue-specific manner and hence their contribution to placental P-gp should be explored. 

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