title: 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 mostly 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 maximum-effect (Emax) functions adequately described temporal changes in the milk/plasma ratio. The median estimated absolute and relative cumulative infant doses were 4.5 mg/kg of body weight (95% prediction interval, 0.6 to 7.0 mg/kg) and 15.7% (95% prediction interval, 2.0 to 27.8%) of the maternal dose, respectively; the latter exceeded 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. (This study has been registered at ClinicalTrials.gov under registration no. NCT01800942.).
authors.affiliation: School of Medicine and Pharmacology, University of Western Australia, Fremantle Hospital, Fremantle, Western Australia, Australia.
authors.forename: Sam
authors.identifier: http://orcid.org/0000-0002-8276-6784
authors.initials: S
authors.lastname: Salman
authors.affiliation: School of Medicine and Pharmacology, University of Western Australia, Fremantle Hospital, Fremantle, Western Australia, Australia tim.davis@uwa.edu.au.
authors.forename: Timothy M E
authors.initials: TM
authors.lastname: Davis
authors.affiliation: School of Pharmacy and Curtin Health Innovation Research Institute, Curtin University of Technology, Perth, Western Australia, Australia.
authors.forename: Madhu
authors.initials: M
authors.lastname: Page-Sharp
authors.affiliation: Medical Research Council Unit, Fajara, The Gambia.
authors.forename: Bully
authors.initials: B
authors.lastname: Camara
authors.affiliation: Medical Research Council Unit, Fajara, The Gambia.
authors.forename: Claire
authors.initials: C
authors.lastname: Oluwalana
authors.affiliation: Medical Research Council Unit, Fajara, The Gambia.
authors.forename: Abdoulie
authors.initials: A
authors.lastname: Bojang
authors.affiliation: Medical Research Council Unit, Fajara, The Gambia London School of Hygiene and Tropical Medicine, London, United Kingdom Institute of Tropical Medicine, Antwerp, Belgium.
authors.forename: Umberto
authors.initials: U
authors.lastname: D'Alessandro
authors.affiliation: Medical Research Council Unit, Fajara, The Gambia London School of Hygiene and Tropical Medicine, London, United Kingdom.
authors.forename: Anna
authors.initials: A
authors.lastname: Roca
mesh_terms: D000328:Adult; D000962:Antimalarials / Q000009:adverse effects / Q000493:pharmacokinetics*; D017963:Azithromycin / Q000009:adverse effects / Q000493:pharmacokinetics*; D002853:Chromatography, Liquid; D004311:Double-Blind Method; D005260:Female; D005714:Gambia / Q000453:epidemiology; D006801:Humans; D013058:Mass Spectrometry; D018811:Maternal Exposure; D008895:Milk, Human / Q000737:chemistry* / Q000378:metabolism; D010919:Placebos; D011247:Pregnancy; D011295:Prenatal Care; D046248:Pyloric Stenosis, Hypertrophic / Q000139:chemically induced / Q000453:epidemiology; D055815:Young Adult
chemical_list: D000962:Antimalarials; D010919:Placebos; D017963:Azithromycin