Perindopril in Breast Milk and Determination of Breastfed Infant Exposure: A Prospective Observational Study

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.

Keywords:

• perindopril
• perindoprilat
• LC-MS/MS
• human plasma
• human milk
• clinical lactation
• infant drug exposure

Details of Ethics Approval

The ethics application of Evaluation of Medicines in Breast Milk and Clinical Effects in the Breastfed Infant (HREC/14/WCHN/115) was granted full ethics approval on 12th Nov, 2014. The ethics application meets the requirements of the National Statement on Ethical Conduct in Human Research and the study was conducted in accordance with the Declaration of Helsinki.

Author Contributions

All authors contributed to data analysis, drafting or revising the article, gave final approval of the version to be published, and agree to be accountable for all aspects of the work.

Disclosure

The authors report no conflicts of interest in this work.