Pharmacokinetics of transfer of piperaquine into the breast milk of Melanesian mothers
- Author(s)
- Moore, BR; Salman, S; Benjamin, J; Page-Sharp, M; Yadi, G; Batty, KT; Siba, PM; Mueller, I; Davis, TM;
- Journal Title
- Antimicrobial Agents and Chemotherapy
- Publication Type
- Journal Article in press
- Abstract
- Transfer of piperaquine (PQ) into breast milk was examined in 27 Papua New Guinean women given a three-day course of dihydroartemisinin-PQ or sulfadoxine-pyrimethamine-PQ during the second/third trimester. Breast milk was sampled on Days 1, 2, 3-5, 7-11 and 14-17 post-delivery, a median (range) of 70 (6-145) days post-dose. A blood sample was taken at delivery and additional serial samples were available in 9 women who delivered within 42 days of dosing. Milk and plasma PQ was assayed by high performance liquid chromatography. A population-based approach was used to model 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/day) was similar to the accepted value of 150 mL/kg/day. The median estimated absolute and relative cumulative infant PQ doses were 22 mug and 0.07%, respectively, corresponding to absolute and relative daily doses of 0.41mug/kg and 0.004%. Model-based simulations for PQ treatment regimens given at birth, 1 week post-delivery and 6 weeks post-delivery showed that the highest median estimated relative total infant dose (0.36%, or median absolute total dose 101 mug/kg) was seen after maternal PQ treatment 6 weeks postpartum. The maximum simulated relative total and daily dose from any scenario were 4.3% and 2.5%, respectively, lower than the recommended 10% upper limit. Piperaquine is transferred into breast milk after maternal treatment doses but PQ exposure in suckling infants appears safe.
- Publisher
- ASM
- Research Division(s)
- Population Health And Immunity
- PubMed ID
- 25963980
- Publisher's Version
- https://doi.org/10.1128/AAC.00327-15
- NHMRC Grants
- NHMRC/634343, NHMRC/1036951, NHMRC/1043345, NHMRC/572561, NHMRC/1016443,
- Terms of Use/Rights Notice
- Refer to copyright notice on published article.
Creation Date: 2015-05-22 11:19:38
Last Modified: 2019-04-01 09:01:18