Pitfalls of Maternal Physiology and Placental Transfer
Substantial changes in maternal physiology complicate the extrapolation
of the safety profile and dosing of drugs. Changes in the
cardiovascular, renal, and gastrointestinal systems affect the
absorption, distribution and excretion of certain drugs given to the
pregnant woman during pregnancy [13]. There is no doubt that drug
pharmacokinetics are different in pregnancy and non-pregnant state and,
ideally, drug properties should be studied in every trimester and in the
postpartum period. However, these trials are challenging to conduct, and
the information is scarce, which is why researchers often rely on
opportunistic studies in which patient are already receiving the
therapeutic agent in question [14, 15]. In addition to that, the
placenta was thought to be an impenetrable barrier that protected the
fetus from harmful agents including medication. However, after the
thalidomide incident, challenges have been unearthed to explore
mechanisms of transfer of compounds across the lipid membrane [16].
Several mechanisms have been proposed to explain the drug transfer
across the placenta including simple diffusion, facilitated diffusion,
pinocytosis, and active transport. Ongoing research is crucial in
identifying potential drugs that follow the trajectory of maternal to
fetal transfer, and the molecular characteristics of compounds.
Uncharged lipophilic drugs tend to transfer readily [17], whereas
size does not usually limit transfer as most drugs have a molecular
weight of less than 500 Daltons [18].Insulin and enoxaparin are two
examples of drug transfers that are limited due to size [19, 20].
Human placental drug transfer studies are often limited to drugs given
near time of delivery. This limitation to study design led to
development of ex vivo perfused human placental models which represented
a non-invasive and effective method of studying transplacental transfer
[21].