The binding of acetaminophen, lidocaine, and valproic acid to pooled normal mature human milk was studied in vitro by using equilibrium dialysis. Scatchard analysis revealed high-affinity, low-capacity binding for acetaminophen (Ka [affinity constant of association], 1.47 x 10(4) L/mol; Bo [concentration of binding sites], 9.01 x 10(-4) mol/L) and some minimal, nonspecific binding. Binding ranged up to 85%. For lidocaine, low-affinity, high-capacity binding was noted (Ka, 1.42 x 10(2) L/mol; Bo, 1.69 x 10(-2) mol/L). Binding ranged up to 72%. For valproic acid, only minimal, nonspecific binding was noted at low drug concentrations with binding ranging up to 64%. The binding of these drugs to milk might enhance their excretion and subsequent ingestion by infants who are breast-fed. In addition, the low pH of the milk (6.24) may cause "ion trapping" of acetaminophen (pKa, 9.5) and lidocaine (pKa, 7.9).