Pharmacokinetics of piperaquine transfer into the breast milk of Melanesian mothers

Moore, Brioni R., Salman, Sam, Benjamin, John, Page-Sharp, Madhu, Yadi, Gumal, Batty, Kevin T., Siba, Peter M., Mueller, Ivo, and Davis, Timothy M.E. (2015) Pharmacokinetics of piperaquine transfer into the breast milk of Melanesian mothers. Antimicrobial Agents and Chemotherapy, 59 (7). pp. 4272-4278.

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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 log(e)(plasma) and milk concentration-time data. A sigmoid E-max 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 mu g and 0.07%, respectively, corresponding to absolute and relative daily doses of 0.41 mu g/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 mu g/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.

Item ID: 42042
Item Type: Article (Research - C1)
ISSN: 1098-6596
Funders: National Health and Medical Research Council of Australia (NHMRC)., Fogarty International Center
Projects and Grants: NHMRC 634343, NHMRC 1036951, NHMRC 1016443, NHMRC 1043345, NHMRC 572761
Date Deposited: 08 Dec 2015 18:32
FoR Codes: 11 MEDICAL AND HEALTH SCIENCES > 1108 Medical Microbiology > 110803 Medical Parasitology @ 100%
SEO Codes: 92 HEALTH > 9204 Public Health (excl. Specific Population Health) > 920404 Disease Distribution and Transmission (incl. Surveillance and Response) @ 100%
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