Infant exposure to dioxin-like compounds in breast milk.

Background: Very little is known about the level of infant exposure to many drugs commonly used during breastfeeding. The aim of this study was to develop a physiologically-based pharmacokinetic (PBPK) model for predicting infant exposure to maternal efavirenz through breastmilk. Methods: A breastfeeding PBPK model combining whole-body maternal and infant sub-models was constructed from drug-specific and system parameters affecting drug disposition using mathematical descriptions. The model was validated against published data on the pharmacokinetics of efavirenz in nursing mother-infant pairs. Further simulations were conducted to assess exposure in the context of the 400 mg reduced dose of efavirenz as well as best- and worse-case scenarios. Results: The model adequately described efavirenz pharmacokinetics, with over 80% of observed data points (203 matched breast milk and plasma pairs) within the predictive interval. All parameters were within 2-fold difference of clinical data. Median (range) predicted versus observed breast milk AUC0-24, Cmax and Cmin at the standard 600 mg dose were 75.0 (18.5-324) versus 68.5 (26.3-257) µg.hr/mL, 4.56 (1.17-16.0) versus 5.39 (1.43-18.4) µg/mL, and 2.11 (0.38-12.3) versus 1.68 (0.316-9.57) µg/mL, respectively. Predicted plasma AUC0-24, Cmax and Cmin at 400 mg reduced dose were similar to clinical data from non-breastfeeding adults. Model-predicted infant plasma concentrations were similar to clinical data, 0.15 (0.026–0.78) μg/mL at the 400 mg maternal dose in pooled analysis, approximately 25% lower than simulated exposure at 600 mg. The maximum exposure index was observed in the youngest infants, 5.9% (2.2-20) at 400 mg and 8.7% (3.2-29) at 600 mg. Thirteen and 36% of 10 days-1 month old infants were predicted to have exposure index above the 10% recommended threshold at 400 mg and 600 mg maternal dose, respectively. Conclusions: This application of PBPK modelling opens up opportunities for expanding our understanding of infant exposure to maternal drugs through breastfeeding.

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Testing for Polychlorinated Biphenyls in Human Milk

PEDIATRICS ◽

10.1542/peds.68.3.411 ◽

1981 ◽

Vol 68 (3) ◽

pp. 411-415

Author(s):

Thomas M. Wickizer ◽

Lawrence B. Brilliant

Keyword(s):

Breast Milk ◽

Polychlorinated Biphenyls ◽

Human Milk ◽

Breast Feeding ◽

Milk Fat ◽

Polychlorinated Biphenyl ◽

Current Data ◽

High Exposure ◽

Infant Exposure ◽

Nursing Mothers

Reports of polychlorinated biphenyl (PCB) contamination of human milk have raised questions about the possible risks of breast-feeding and whether nursing mothers ought to have their breast milk tested. Current data on contamination of human milk are needed so that pediatricians can make informed recommendations about breast milk testing and breast-feeding. With consideration of recent findings of PCB contamination of human milk in Michigan, recommendations concerning breast milk testing and breast-feeding are made. No major changes in current breast-feeding practices are advised. However, breast milk testing is recommended for certain nursing mothers who have had potentially high exposure to PCBs. Limiting the duration of breast-feeding may also be advisable for mothers with high PCB milk fat levels in order to reduce infant exposure to PCBs.

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Limited infant exposure to benznidazole through breast milk during maternal treatment for Chagas disease

Archives of Disease in Childhood ◽

10.1136/archdischild-2014-306358 ◽

2014 ◽

Vol 100 (1) ◽

pp. 90-94 ◽

Cited By ~ 17

Author(s):

Facundo García-Bournissen ◽

Samanta Moroni ◽

Maria Elena Marson ◽

Guillermo Moscatelli ◽

Guido Mastrantonio ◽

...

Keyword(s):

Breast Milk ◽

Chagas Disease ◽

High Performance ◽

Adverse Drug Events ◽

Disease Treatment ◽

Lactating Women ◽

Infant Exposure ◽

Breastfed Infants ◽

Link Type ◽

Registration Number

BackgroundBenznidazole (BNZ) is safe and effective for the treatment of paediatric Chagas disease. Treatment of adults is also effective in many cases, but discouraged in breastfeeding women because no information on BNZ transfer into breast milk is available. We aimed to evaluate the degree of BNZ transfer into breast milk in lactating women with Chagas disease.Patients and methodsProspective cohort study of lactating women with Chagas disease treated with BNZ administered for 30 days. Patients and their breastfed infants were evaluated at admission, the 7th and 30th day of treatment (and monthly thereafter, for 6 months). BNZ was measured in plasma and milk by high performance liquid chromatography. The protocol was registered in ClinicalTrials.gov (#NCT01547533).Results12 lactating women with chronic Chagas disease were enrolled (median age 28.5 years, range 20–34). Median BNZ dose was 5.65 mg/kg/day twice daily. Five mothers had adverse drug events (45%), but no adverse drug reactions or any untoward outcomes were observed in the breastfed infants. Median milk BNZ concentration was 3.8 mg/L (range 0.3–5.9) and 6.26 mg/L (range 0.3–12.6) in plasma. Median BNZ milk to plasma ratio was 0.52 (range 0.3–2.79). Median relative BNZ dose received by the infant (assuming a daily breast milk intake of 150 mL/kg/day) was 12.3% of the maternal dose per kg (range 5.5%–17%).ConclusionsThe limited transference of BNZ into breast milk and the reassuring normal clinical evaluation of the breastfed babies suggest that maternal BNZ treatment for Chagas disease during breast feeding is unlikely to present a risk for the breastfed infant.Trial registration numberClinicalTrials.gov NCT01547533.

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