Transfer of drugs into breast milk is bidirectional, reflecting passive diffusion of unbound drug between plasma and blood, rather than active secretion. Factors that affect the milk concentration include binding to maternal plasma proteins, protein binding in milk, lipid content of milk, and physiochemical factors of the drug (109). As shown in Figure 22.7, drug concentrations in breast milk are usually less than plasma concentrations are and there usually is a fixed ratio between milk and plasma concentrations (110). Concentration-dependent saturation of the plasma protein binding precludes calculation of a fixed milk:plasma ratio for a few drugs (Figure 22.8) (111). However, in the usual case, drug concentrations measured in plasma and breast milk are used to calculate a milk:plasma ratio (M/P), from which the daily drug dose to the infant is estimated as follows:
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