title: Pharmacokinetics of piperaquine transfer into the breast milk of Melanesian mothers.
abstract: Transfer of piperaquine (PQ) into breast milk was examined in 27 Papua New Guinean women given a 3-day course of dihydroartemisinin-PQ or sulfadoxine-pyrimethamine-PQ during the second/third trimester. Breast milk was sampled on days 1, 2, 3 to 5, 7 to 11, and 14 to 17 postdelivery, a median of 70 days postdose (range, 6 to 145 days). A blood sample was taken at delivery, and additional serial samples were available from 9 women who delivered within 42 days of dosing. Milk and plasma PQ were assayed by high-performance liquid chromatography. A population-based approach was used to model the loge(plasma) and milk concentration-time data. A sigmoid Emax model best described PQ breast milk transfer. The population average milk:plasma PQ ratio was 0.58, with a peak of 2.5 at delivery. The model-derived maximum milk intake (148 ml/kg of body weight/day) was similar to the accepted value of 150 ml/kg/day. The median estimated absolute and relative cumulative infant PQ doses were 22 μg and 0.07%, respectively, corresponding to absolute and relative daily doses of 0.41 μg/kg and 0.004%. Model-based simulations for PQ treatment regimens given at birth, 1 week postdelivery, and 6 weeks postdelivery showed that the highest median estimated relative total infant dose (0.36%; median absolute total dose of 101 μg/kg) was seen after maternal PQ treatment 6 weeks postpartum. The maximum simulated relative total and daily doses from any scenario were 4.3% and 2.5%, respectively, which were lower than the recommended 10% upper limit. Piperaquine is transferred into breast milk after maternal treatment doses, but PQ exposure for suckling infants appears safe.
authors.affiliation: School of Medicine and Pharmacology, University of Western Australia, Fremantle Hospital, Western Australia, Australia Papua New Guinea Institute of Medical Research, Madang, Papua New Guinea.
authors.forename: Brioni R
authors.initials: BR
authors.lastname: Moore
authors.affiliation: School of Medicine and Pharmacology, University of Western Australia, Fremantle Hospital, Western Australia, Australia.
authors.forename: Sam
authors.initials: S
authors.lastname: Salman
authors.affiliation: Papua New Guinea Institute of Medical Research, Madang, Papua New Guinea.
authors.forename: John
authors.initials: J
authors.lastname: Benjamin
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: Papua New Guinea Institute of Medical Research, Madang, Papua New Guinea.
authors.forename: Gumal
authors.initials: G
authors.lastname: Yadi
authors.affiliation: School of Pharmacy and Curtin Health Innovation Research Institute, Curtin University of Technology, Perth, Western Australia, Australia.
authors.forename: Kevin T
authors.initials: KT
authors.lastname: Batty
authors.affiliation: Papua New Guinea Institute of Medical Research, Madang, Papua New Guinea Department of Microbiology, Division of Veterinary and Biomedical Sciences, James Cook University, Townsville, Australia.
authors.forename: Peter M
authors.initials: PM
authors.lastname: Siba
authors.affiliation: Infection and Immunity Division, Walter and Eliza Hall Institute, Parkville, Victoria, Australia Center de Recerca en Salut Internacional de Barcelona, Barcelona, Spain.
authors.forename: Ivo
authors.initials: I
authors.lastname: Mueller
authors.affiliation: School of Medicine and Pharmacology, University of Western Australia, Fremantle Hospital, Western Australia, Australia tim.davis@uwa.edu.au.
authors.forename: Timothy M E
authors.initials: TM
authors.lastname: Davis
mesh_terms: D000328:Adult; D000375:Aging / Q000378:metabolism; D000962:Antimalarials / Q000009:adverse effects / Q000493:pharmacokinetics*; D002851:Chromatography, High Pressure Liquid; D003198:Computer Simulation; D005260:Female; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008542:Melanesia; D008895:Milk, Human / Q000378:metabolism*; D008954:Models, Biological; D049590:Postpartum Period; D011804:Quinolines / Q000009:adverse effects / Q000493:pharmacokinetics*; D055815:Young Adult; D010879:Piperazines
chemical_list: D000962:Antimalarials; D011804:Quinolines; C034759:piperaquine; D010879:Piperazines