Pharmacokinetics of transfer of azithromycin into the breast milk of African mothers

Abstract

Azithromycin (AZI) is used for its antibiotic and antimalarial properties in pregnancy. Reported estimates of AZI breast milk transfer, based on concentrations in single samples from small numbers of women, have suggested that infant intake is safe. To better characterize infant intake and the associated potential benefits and risks, AZI was measured by liquid chromatography-mass spectrometry in four breast milk samples taken over 28 days postpartum from each of 20 Gambian women given 2 g AZI during labor. A population pharmacokinetic model utilizing published parameters for AZI disposition in pregnancy, the present breast milk concentrations, and increasing/decreasing sigmoid Emax functions, adequately described temporal changes in the milk:plasma ratio. The median estimated absolute and relative cumulative infant doses were 4.5 (95% prediction interval 0.6-7.0) mg/kg and 15.7 (95% prediction interval 2.0-27.8) % of maternal dose, respectively, the latter exceeding the recommended 10% safety limit. Although some infants with bacterial infections may benefit from AZI in breast milk, there is a risk of hypertrophic pyloric stenosis with a worst-case number needed to harm of 60 based on the present and available epidemiologic data.