Maternal Plasma Concentrations
Drugs enter, and in almost all cases exit, breast milk in a direct relation to the concentration of the medication in maternal plasma. The higher the milk/plasma (M/P) ratio, the greater the amount of the drug found in breast milk. When the maternal plasma concentration of a medication falls below its concentration in breast milk, equilibrium forces drive the medication out of the breast milk and back into the maternal plasma for elimination (Hale, 2002). The M/P ratio gives an estimate of a drug's distribution between maternal milk and plasma. A M/P ratio greater than 1.0 suggests that the drug may be sequestered in breast milk in high concentrations. For example, a M/P ratio of 4.0 means that the concentration of the medication in breast milk is four times higher than it is in maternal plasma (Riordan & Auerbach, 1998), whereas a M/P ratio less than 1.0 is considered low and is indicative that only low drug concentrations will be transferred into breast milk. While it is best to choose drugs with low M/P ratios, a high M/P ratio does not necessarily contraindicate the use of a particular medication by a breastfeeding mother (Hale, 2002). This is because the M/P ratio does not provide all of the information about the absolute amount of a drug that can be transferred to the infant from breast milk (Hale, 2002). Even if the medication has a high M/P ratio, if the maternal plasma concentration of the drug is minute, then the absolute amount (i.e., dose) of a drug entering breast milk will likely be small enough to be considered subclinical for the infant (Hale, 2002). Thus, higher M/P ratios can be misleading because they can provide the impression that large amounts of a medication are transferred into breast milk, and this may not be the case if the maternal dosage is low.
The pKa of a drug is the pH at which a drug exists equally in ionic and nonionic states. Drugs that have a pKa higher than 7.2 may be sequestered in breast milk to a slightly higher degree than those with a lower pKa (Hale, 2002). This occurs when the nonionized molecule of a high pKa (i.e., weakly basic) drug enters breast milk, is quickly ionized, and then is prevented from diffusing out of breast milk back into the maternal circulation. Thus, the drug is "trapped" in its ionized form and accumulates in the breast milk at high M/P ratios. Since drugs that have a higher pKa tend to have higher M/P ratios, medications with a lower pKa are favored for breastfeeding women (Hale, 2002).
J Pediatr Health Care. 2003;17(6) © 2003 Mosby, Inc.
Cite this: Medications and Lactation: What PNPs Need to Know - Medscape - Nov 01, 2003.
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