Drug interactions at the human placenta: What is the evidence?

Miriam Rubinchik-Stern, Sara Eyal*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

49 Scopus citations

Abstract

Pregnant women (and their fetuses) are treated with a significant number of prescription and non-prescription medications. Interactions among those drugs may affect their efficacy and toxicity in both mother and fetus. Whereas interactions that result in altered drug concentrations in maternal plasma are detectable, those involving modulation of placental transfer mechanisms are rarely reflected by altered drug concentrations in maternal plasma. Therefore, they are often overlooked. Placental-mediated interactions are possible because the placenta is not only a passive diffusional barrier, but also expresses a variety of influx and efflux transporters and drug-metabolizing enzymes. Current data on placental-mediated drug interactions are limited. In rodents, pharmacological or genetic manipulations of placental transporters significantly affect fetal drug exposure. In contrast, studies in human placentae suggest that the magnitude of such interactions is modest in most cases. Nevertheless, under certain circumstances, such interactions may be of clinical significance.This review describes currently known mechanisms of placental-mediated drug interactions and the potential implications of such interactions in humans. Better understanding of those mechanisms is important for minimizing fetal toxicity from drugs while improving their efficacy when directed to treat the fetus.

Original languageAmerican English
Article numberArticle 126
JournalFrontiers in Pharmacology
Volume3 JUL
DOIs
StatePublished - 2012

Keywords

  • Breast cancer resistance protein
  • Drug interactions
  • Maternal-fetal pharmacology
  • Organic cation transporters
  • P-glycoprotein
  • Placenta
  • Pregnancy

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