Pharmaceutical Research

, 35:71 | Cite as

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

  • Nino Tetro
  • Sonia Moushaev
  • Miriam Rubinchik-Stern
  • Sara Eyal
Expert Review Theme: The Use of Pharmaceuticals in Pregnancy and Lactation
Part of the following topical collections:
  1. The Use of Pharmaceuticals in Pregnancy and Lactation

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.

KEY WORDS

drug transporters maternal-fetal pharmacology placenta placental transfer pregnancy 

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

Notes

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.

Compliance with ethical standards

The authors have no commercial or financial relationships that could be constructed as a potential conflict of interest.

Supplementary material

11095_2017_2286_MOESM1_ESM.docx (46 kb)
ESM 1 (DOCX 45 kb)

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© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Institute for Drug Research, School of PharmacyThe Hebrew University of JerusalemJerusalemIsrael

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