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Peter J. Brodhead | Jan 6, 2015

Why Do Some Drugs Cross the Placental Barrier More Than Others?

Categories: Zofran, Birth Injury

We use the term “placental barrier” here because a lot of drug companies refer to it in their package inserts. While there is no true “barrier” between the mother and her fetus, there is a semipermeable membrane made up of placental tissues that limit the kind and amount of material that can be passed along from the mother.

The fact is that most drugs do cross the placenta in some amount. The better question, therefore, is: How muchof a given drug crosses the placenta? For a drug to be teratogenic in pregnancy, it must be able to cross the placenta in early pregnancy in a concentration high enough to cause abnormal fetus development. Drug companies have known for a long time that there are certain characteristics of their drug that will determine how much of it crosses the placenta.

The primary determining factors of what type of drugs will cross the placental barrier are molecular weight, lipid (fat or fat-like) solubility, polarity (molecular charge), protein binding, and receptor mediation. Drugs that have low molecular weight, lipid (fat) solubility, nonpolarity, and no protein binding properties will quickly and easily cross the placenta.

Alcohol, for example, readily reaches the embryo in fairly high concentrations. On the other hand, high molecular-weight drugs like heparin (20,000 daltons) do not cross the placenta. It is therefore widely used to treat hypercoagulation during pregnancy.

Zofran (ondansetron) has properties that cause it to easily cross the placenta in substantial amounts. Just for example, it has great lipid solubility, low molecular weight (365.9 daltons), and a measured in vitro plasma protein binding of 70% to 76%. In a medical study specifically designed to quantify the placental transfer of Zofran (ondansetron) in the first trimester of human pregnancy, Zofran was found in all embryonic compartments and in an average concentration of 41% of the corresponding concentration in maternal plasma.

Zofran has now been shown to significantly increase the risk of birth defects in pregnant mothers who take it during the first trimester.