Analgesie drugs in breast milk and plasma*

Abstract

The possible excretion of drugs in breast milk frequently prompts questions about the safety of the infant in continued nursing during periods of drug treatment of the mother. The disposition of salicylic acid, phenacetin, caffeine and codeine and 2 metabolites, acetaminophen and morphine was studied in breast milk and plasma of 2 lactating mothers after single oral doses of a compound analgesic. Salicylic acid penetrated poorly into milk, with peak levels of only 1.12-1.69 .mu.g/ml; peak plasma levels were 33-43.4 .mu.g/ml. The drug was eliminated more slowly from milk than plasma. Caffeine and phenacetin kinetics in breast milk and plasma were similar, but milk levels were somewhat lower than plasma levels in both subjects. Metabolically produced acetaminophen levels in both fluids were much higher than those of the parent drug, phenacetin, in 1 subject, but early plasma and milk phenacetin levels exceeded those of acetaminophen in the other subject, thereafter dropping sharply to assume the pattern of the 1st subject. Elimination of the metabolite, acetaminophen, from milk was slower than from plasma (subject 1, half-life (t1/2) of drug in milk, 4.7 h; t1/2 in plasma, 2.9 h). In both subjects codeine concentrations in milk were 1.5-2.4 times as high as in plasma at the same times after drug. Metabolically produced morphine levels in milk from both mothers were low but exceeded those in plasma after 1 h. Calculations based on average milk concentrations over the 12 h after drug in subject 1 revealed milk excretion of 0.7% or less of the ingested dose of each drug. Similar calculations based on predicted steady-state milk drug concentrations in subject 2 indicated maximum milk excretion of 2.7% of the dose. In each case caffeine was excreted in the milk in the greatest amount.