Placenta, drug transfer across

Garland M. Pharmacology of drug transfer across the placenta. Obstet Gynecol Clin North Am 1998 25 21-42. 

Gases, nutrients, hormones, electrolytes, antibodies and waste products are transported across the placenta. Many drugs and infectious agents can also cross the placenta. Maternal transfer of steroid hormones across the placenta is limited. When natural or synthetic steroid hormones do cross the placenta, developmental toxicity can result. Furthermore, hormones produced by the fetal placenta also play an important role in parturition. 

If drugs are transferred across the placenta, they may be potentially hazardous to the fetus. Drugs primarily cross the placenta by passive diffusion. Lipid-soluble, unionized drugs can enter the fetal bloodstream. The fetal bloodstream is protected from drugs that are relatively lipid insoluble and/or highly ionized in plasma. However, the fetus is, at least to some extent, exposed to essentially all drugs administered to the pregnant mare. 

Lipid-soluble drugs diffuse easily across the placenta, whereas water-soluble ones pass through at slower rates. Although the placenta is relatively impermeable to polar compounds, some transfer will occur if a sufficiently high maternal-fetal concentration gradient exists and sufficient time is allowed (Pacifici and Nottoli 1995). 

Because vigabatrin is not protein-bound and is a highly water-soluble compound, a wide distribution in the body is observed [63], and readily crosses the BBB. CSF concentrations are about 10-15% of those in plasma [62, 64], It has a volume of distribution of about 0.8 1/kg [65-68]. It distributes into red blood cells and saliva at a concentration of 30-80% and 10% of that in the plasma, respectively [69]. The transfer of the drug from maternal to fetal blood across the placenta was low and was... 

Distribution addresses the transfer of the drug compound from the site of administration to the systemic circulation and then to bodily tissues. Both in vitro and in vivo studies are informative here. In vitro studies, for example, examine plasma protein binding. In vivo studies use whole body autoradiography that can display visually how much drug has reached different parts of the body. Transfer of the drug compound in milk to an infant and across the placenta is also studied. 

---