Current toxicological aspects on drug and chemical transport and metabolism across the human placental barrier.
BACKGROUND
Placenta plays an obligatory role in fetal growth and development by performing a multitude of functions, including embryo implantation, transport of nutrients and elimination of metabolic waste products and endocrine activity. Drugs and chemicals can transfer across the placental barrier from mother to fetus either by passive diffusion mechanisms and/or via a network of active transporters, which may lead to potential fetotoxicity effects. Placenta also expresses a wide variety of enzymes, being capable of metabolizing a large diversity of drugs and chemicals to metabolites of lower or even higher toxicity than parent compounds.


METHODS
The present review aims to summarize the current toxicological aspects in the emerging topic of drug transport and metabolism across the human placental barrier.


CONCLUSIONS
There is an emerging demand for accurate assessment of drug transport and metabolism across the human placental barrier, on the basis of a high throughput screening process in the early stages of drug design, to avoid drug candidates from potential fetotoxicity effects. In this aspect, combined studies, which take into account in vivo and in vitro investigations, as well as the ex vivo perfusion method and the recently developed computer-aided technologies, may significantly contribute to this direction.
University of the Aegean, Department of Food Science and Nutrition, 2 Mitropoliti Ioakeim Street, Myrina, Lemnos 81400, Greece. cgiaginis@aegean.gr
Constantinos
C
Giaginis
Stamatios
S
Theocharis
Anna
A
Tsantili-Kakoulidou
D000818:Animals; D001692:Biological Transport; D015195:Drug Design; D064420:Drug-Related Side Effects and Adverse Reactions; D005260:Female; D047109:Fetal Development / Q000187:drug effects; D006801:Humans; D008431:Maternal-Fetal Exchange; D010477:Perfusion; D004364:Pharmaceutical Preparations / Q000378:metabolism*; D010920:Placenta / Q000378:metabolism*; D011247:Pregnancy; D018570:Risk Assessment
D004364:Pharmaceutical Preparations