<p>Perindopril in Breast Milk and Determination of Breastfed Infant Exposure: A Prospective Observational Study</p>

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.

Infant Exposure to Armodafinil Through Human Milk Following Maternal Use of Modafinil

“…The methods for the collection and analysis of human milk and plasma samples were consistent with those described in our previous research (Leggett et al, 2020;. During the study period, the participant took modafinil 300 mg at 9 a.m. and 100 mg at 12:30 p.m. on Day 1, and 300 mg at 9:30 a.m. and 100 mg at 1 p.m. on Day 2.…”

Response to Dr. Anderson’s Letter to the Editor: Modafinil and Armodafinil in Human Milk

“…In this case study, it was not practical to take multiple maternal plasma samples over the 24-hr dosing period as the participant was not an inpatient. We have described the limitations of calculating the M/P ratio from a single time point in our previous publications (Leggett et al, 2020; Lwin, Gerber, et al, 2018; Lwin, Leggett, et al, 2018). In the current case study, we have not relied upon the M/P ratio in our interpretation and rationale for the safety of modafinil in breastfeeding as its clinical relevance may be limited.…”