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Are drugs that have a tendency to become ion-trapped (high pKa value) permanently trapped in the milk compartment, or do they simply take longer to transfer out? For instance, if a mother didn’t pump and discard her milk but observed the recommended waiting period, would her milk be free of the drug after that time had passed?
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Hi JCW1031,
Ion trapping is a fascinating phenomenon. As neat as it is biochemically speaking…clinically I haven’t seen it result in issues in lactation pharmacology to the level we worry about theoretically. It probably contributes to higher concentrations of barbiturates. For ion trapping to occur the drug must first 1) be present in the serum and 2) meet parameters for passive diffusion. For us, it isn’t common to find a drug with these issues that is also orally bioavailable and potentially harmful to the infant. Not to say it isn’t possible, just that we haven’t really observed it much.
I think the terminology is a little misleading. Ion “trapping” correctly implies that more drug will be in the milk than expected. However, it is still an equilibrium -- a bidirectional balance. As drug concentrations fall in serum, milk levels still fall in the milk. It will take longer for the drug to clear without pumping and discarding, but it does not stay indefinitely. Depending on the drug, it may also degrade while in the milk compartment.
Here’s a snippet in Dr. Hale and I's textbook chapter for Polin’s Fetal and Neonatal Physiology:
"The degree of ionization (pKa) of a drug is a unique physicochemical property that controls its ionization state when in solution. If the drug's pKa is the same as the pH of the solution it is dissolved in, then 50% of the drug exists ionized and 50% exists nonionized. As the pH of the solution changes, the state of ionization changes as well. Because the pH of milk (7.2) is lower than that of plasma (7.4), drugs with a pKa > 7.4 will partially ionize in the milk compartment. Ionized compounds are less lipophilic and are less able to pass through a lipid bilayer. The newly ionized form of the drug may have difficulty diffusing back out of the milk. Thus, the ion trapping phenomenon can significantly elevate milk drug concentrations above what is expected from passive diffusion alone."
Kaytlin -
Thank you Kaytlin, that makes a lot of sense. So for a very hazardous, high-pKa drug like cocaine, is the recommended 24-hour waiting period still enough time to clear the milk if a mother doesn’t pump and discard in the interim?Comment
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Yes - the half life of cocaine itself is very short. There is a metabolite that is used to evaluate cocaine consumption with a much longer half life (benzoylecgonine), but it is inactive.
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