Propranolol, Propranolol Glucuronide, and Naphthoxylactic Acid in Breast Milk and Plasma

Abstract

High-performance liquid chromatographic assays for propranolol [used for the treatment of hypertension] and its major metabolites in plasma and breast milk are described. The breast milk/whole plasma ratios of propranolol in 3 lactating women were in the range of 0.33-1.65. The half-life (t1/2) of elimination of propranolol from breast milk was 6.5 .+-. 3.4 h (mean .+-. SD), which was significantly longer (t [test of significance] = 1.844, df [degrees of freedom] = 4, P < 0.01) than the t1/2 of elimination of propranolol from plasma, which was 2.6 .+-. 1.2 h (mean .+-. SD). The t1/2 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 > 0.05) from the mean t1/2 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 ingested as either propranolol or as propranolol glucuronide in breast milk by the neonate would be < 0.1% of the maternal dose.