Catherine Leggett1, Ei Mon Phyo Lwin2, Usha Ritchie1, Yunmei Song2, Jacobus P Gerber2, Sean Turner1, William M Hague3,4, Michael Stark3,5, Richard Upton2, Sanjay Garg2. 1. SA Pharmacy, Women's and Children's Hospital, North Adelaide, SA 5006, Australia. 2. School of Pharmacy and Medical Sciences, Reid Building, City East Campus, University of South Australia, Adelaide, SA 5000, Australia. 3. Robinson Research Institute, University of Adelaide, North Adelaide, SA 5006, Australia. 4. Obstetric Medicine, Women's and Children's Hospital, North Adelaide, SA 5006, Australia. 5. Neonatal Medicine, Women's and Children's Hospital, North Adelaide, SA 5006, Australia.
Abstract
OBJECTIVE: This study aimed to quantify the amount of perindopril and its active metabolite perindoprilat present in breast milk and corresponding maternal and infant plasma concentrations. DESIGN: Prospective, longitudinal, observational. SETTING: Tertiary specialist paediatric and obstetric hospital in Adelaide, South Australia. POPULATION: Breastfeeding women actively treated with perindopril for hypertensive disorders postpartum. METHODS: Eight breast milk samples and a single plasma sample were collected from each participant over a 24 hrs period, and plasma samples were taken from eligible breastfed infants. Breast milk and plasma concentrations of perindopril and perindoprilat were analysed using a validated Liquid Chromatography tandem-Mass Spectrometry (LC-MS/MS) method. MAIN OUTCOME MEASURES: Mean breast milk concentrations of perindopril and perindoprilat, Relative Infant Dose (RID) <10%, and Theoretical Infant Dose (TID). RESULTS: Ten women and three infants participated in the study. The mean concentration of perindopril in breast milk for each participant ranged from 0.003 to 1.2 ng/mL and perindoprilat 0.2-36 ng/mL. RID for perindopril was 0.0005-0.2% and perindoprilat 0.03-4.6%. TID for perindopril was 0.00045-0.18 µg/kg/day and perindoprilat 0.032-5.4 µg/kg/day. Infant plasma levels for perindopril ranged from 0.44 to 1.12 ng/mL and perindoprilat undetectable - 10.14 ng/mL. Maternal reports described normal infant growth and development. CONCLUSION: Infant exposure to perindopril and perindoprilat through breast milk is low. However, some infants were found to have plasma perindoprilat concentrations consistent with pharmacodynamic effects. Perindopril may be used in mothers of healthy term infants, provided the infant is carefully monitored.
OBJECTIVE: This study aimed to quantify the amount of perindopril and its active metabolite perindoprilat present in breast milk and corresponding maternal and infant plasma concentrations. DESIGN: Prospective, longitudinal, observational. SETTING: Tertiary specialist paediatric and obstetric hospital in Adelaide, South Australia. POPULATION: Breastfeeding women actively treated with perindopril for hypertensive disorders postpartum. METHODS: Eight breast milk samples and a single plasma sample were collected from each participant over a 24 hrs period, and plasma samples were taken from eligible breastfed infants. Breast milk and plasma concentrations of perindopril and perindoprilat were analysed using a validated Liquid Chromatography tandem-Mass Spectrometry (LC-MS/MS) method. MAIN OUTCOME MEASURES: Mean breast milk concentrations of perindopril and perindoprilat, Relative Infant Dose (RID) <10%, and Theoretical Infant Dose (TID). RESULTS: Ten women and three infants participated in the study. The mean concentration of perindopril in breast milk for each participant ranged from 0.003 to 1.2 ng/mL and perindoprilat 0.2-36 ng/mL. RID for perindopril was 0.0005-0.2% and perindoprilat 0.03-4.6%. TID for perindopril was 0.00045-0.18 µg/kg/day and perindoprilat 0.032-5.4 µg/kg/day. Infant plasma levels for perindopril ranged from 0.44 to 1.12 ng/mL and perindoprilat undetectable - 10.14 ng/mL. Maternal reports described normal infant growth and development. CONCLUSION: Infant exposure to perindopril and perindoprilat through breast milk is low. However, some infants were found to have plasma perindoprilat concentrations consistent with pharmacodynamic effects. Perindopril may be used in mothers of healthy term infants, provided the infant is carefully monitored.
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