Propranolol, propranolol glucuronide, and naphthoxylactic acid in breast milk and plasma

High-performance liquid chromatographic assays for propranolol and its major metabolites in plasma and breast milk are described. The breast milk/whole plasma ratios of propranolol in three lactating women were in the range of 0.33 to 1.65. The half-life of elimination of propranolol from breast milk was 6.5 +/- 3.4 h (mean +/- SD), which was significantly longer (t = 1.844, df = 4, p less than 0.01) than the half-life of elimination of propranolol from plasma, which was 2.6 +/- 1.2 h (mean +/- SD). The half-life of elimination of the propranolol metabolite naphthoxylactic acid from breast milk was 4.2 +/- 0.9 h (mean +/- SD), which was not significantly different (t = 0.042, df = 4, p greater than 0.05) from the mean half-life of elimination from plasma, which was 4.2 +/- 1.2 h (mean +/- SD). The penetration of propranolol glucuronide into breast milk was slower and to a lesser extent than that of propranolol and naphthoxylactic acid. The maximum dose, calculated from the results presented in this paper, ingested as either propranolol or as propranolol glucuronide in breast milk by the neonate would be less than 0.1% of the maternal dose.