The Placental Barrier: the Gate and the Fate in Drug Distribution

Abstract

Optimal development of the embryo and the fetus depends on placental passage of gases, nutrients, hormones, and waste products. These molecules are transferred across the placenta via passive diffusion, carrier-mediated cellular uptake and efflux, and transcytosis pathways. The same mechanisms additionally control the rate and extent of transplacental transfer of drugs taken by the pregnant mother. Essentially all drugs cross the placenta to a certain extent, and some accumulate in the placenta itself at levels that can even exceed those in maternal plasma. Hence, even drugs that are not efficiently transferred across the placenta may indirectly affect fetal development by interfering with placental function. In this article, we describe key properties of the placental barrier and their modulation by medications. We highlight implications for pharmacotherapy and novel approaches for drug delivery in pregnant women and their fetuses.

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Abbreviations

ABC:

Adenosine triphosphate binding cassette

BBMVs:

Placental brush-border membrane vesicles

BCRP:

Breast cancer resistance protein

CNT:

Concentrative nucleoside transporter

CYP:

Cytochrome P-450

ENT:

Equilibrative nucleoside transporter

FcRn:

Neonatal Fc receptors

LAT:

L-type amino acid transporter

MDR:

Multidrug resistance protein

MRP:

Multidrug resistance-associated protein

NET:

Norepinephrine transporter

OAT:

Organic anion transporter

OATP:

Organic anion transporting polypeptide

OCT, OCTN:

Organic cation transporter

P-gp:

P-glycoprotein

RFC:

Reduced folate carrier

SERT:

Serotonin transporter

SLC:

Solute carrier

UGT:

Uridine diphosphate glucoronosyltransferase

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ACKNOWLEDGMENTS AND DISCLOSURES

The authors acknowledge the support of the Israel Science Foundation (ISF) Grant 506/13.

Sara Eyal is affiliated with the David R. Bloom Centre for Pharmacy and Dr. Adolf and Klara Brettler Centre for Research in Molecular Pharmacology and Therapeutics at The Hebrew University of Jerusalem, Israel.

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Correspondence to Sara Eyal.

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Dedicated to (late) Dr. Zvi Ben Zvi, Ben Gurion University of the Negev, Beer Sheva, Israel, for his contribution to the field of maternal-fetal pharmacology.

Guest Editor: Sara Eyal

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Tetro, N., Moushaev, S., Rubinchik-Stern, M. et al. The Placental Barrier: the Gate and the Fate in Drug Distribution. Pharm Res 35, 71 (2018). https://doi.org/10.1007/s11095-017-2286-0

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KEY WORDS

  • drug transporters
  • maternal-fetal pharmacology
  • placenta
  • placental transfer
  • pregnancy