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

INTRODUCTION: Narcolepsy, a condition adversely affecting psychological, social, and cognitive function, is more prevalent in females of childbearing age than the general population. Modafinil and armodafinil are central nervous system stimulants approved for treatment of narcolepsy. Infant exposure to these agents through human milk has not been investigated. Poor quality medication safety information during lactation is associated with early cessation of breastfeeding and suboptimal healthcare for the breastfeeding family. MAIN ISSUE: In this case study, we measured the concentration of armodafinil (the most active form of modafinil) in human milk and infant plasma to quantify infant exposure. MANAGEMENT: The participant was a 30-year-old primipara with narcolepsy, taking modafinil (300 mg morning, 100 mg noon) while breastfeeding her 6-week-old infant despite the paucity of safety information. Armodafinil concentrations were measured in eight serial human milk samples collected over a 26-hr period and in single maternal and infant plasma samples using ultra performance liquid chromatography - tandem mass spectrometry. The average concentration of armodafinil in human milk was 1.96 mg/L; the relative infant dose was 4.85%; the theoretical infant dose was 0.294 mg/kg/day. Maternal and infant plasma concentrations of armodafinil were 12.02 mg/L and 0.19 mg/L, respectively. The participant continued to exclusively breastfeed the infant, who had normal growth and development. CONCLUSION: Based on these findings, relatively small amounts of armodafinil pass into human milk, with consequent limited infant exposure. Consideration can be given to the use of modafinil or armodafinil during breastfeeding, provided the infant is monitored. Further studies are needed to confirm these findings.

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

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.

Transfer of rosuvastatin into breast milk: liquid chromatography-mass spectrometry methodology and clinical recommendations.

INTRODUCTION: Rosuvastatin reduces concentrations of total cholesterol (TC) and is used for the management of hypercholesterolemia and prevention of acute coronary syndromes. There are no published reports estimating infant exposure to rosuvastatin through breast milk. PURPOSE: The aims of this study were to quantify concentrations of rosuvastatin in human milk and plasma from a lactating woman taking rosuvastatin and to investigate potential infant exposure. MATERIALS AND METHODS: A 38-year-old breastfeeding mother was commenced on rosuvastatin 20 mg daily for secondary prevention of an acute coronary syndrome. Eight maternal breast milk samples and a single plasma sample were collected over a 24-hour period. The samples were quantified using a sensitive liquid chromatography-mass spectrometry (LC-MS/MS) method. RESULTS: The average concentration of rosuvastatin in breast milk was 30.84 ng/mL, and a peak concentration of 58.59 ng/mL occurred at 17 hours after oral administration. Although the milk-to-plasma (M/P) ratio was 16.49 at 14 hours, the theoretical infant dosage (TID) and relative infant dose (RID) were 0.005 mg/kg/day and 1.50%, respectively. CONCLUSION: The findings suggest that only small amounts of rosuvastatin pass into breast milk. Should the maternal condition necessitate treatment, consideration could be given to the use of rosuvastatin during breastfeeding provided the infant is monitored.

Estimation of Atenolol Transfer Into Milk and Infant Exposure During Its Use in Lactating Women.

BACKGROUND: Atenolol lactation information is limited, and controversy exists over the safety of its use during breastfeeding. In this study, important parameters including milk-to-plasma ratio, ratio of infant plasma to maternal plasma, infant daily dosage, and relative infant dose were investigated. The findings from this study add information to existing data about atenolol transfer in human milk. This may help guide health professionals in decision making regarding the safety of beta blockers used by mothers during breastfeeding. Research aim: The aims of the study were to quantify concentrations of atenolol in human plasma and milk, to evaluate atenolol pharmacokinetics in lactating women, and to investigate subsequent infant exposure to atenolol via mother's milk. METHODS: In this prospective, longitudinal observational study, participants were lactating mothers ( N = 3), 1 to 4 months postpartum, who had been taking atenolol for therapeutic reasons, and one 4-month-old breastfed infant. Eight milk samples were collected over 24 hr at different time points, together with a single blood sample from each lactating mother and the infant, and quantified using a new sensitive liquid chromatography mass spectrometry method developed for this study. RESULTS: Peak milk concentrations of atenolol were observed in the women at 4 hr (Tmax) after oral administration. The dose-normalized maximum concentrations (Cmax) of all patients were similar. The mean milk-to-plasma ratio of the patients who were taking 25 to 100 mg of atenolol was 8.57%. In the mother-infant pair study, the ratio (%) of infant plasma drug concentration to maternal plasma drug concentration observed (18.87%) was similar to the relative infant dose estimated (18.20%). The relative infant dose values (13.96%-18.20%) for all patients were within 10% to 25% of maternal dosage. CONCLUSION: Atenolol use during breastfeeding should be undertaken with some precaution. If clinically indicated, an alternate beta blocker may be preferred.

A new LC-MS/MS bioanalytical method for perindopril and perindoprilat in human plasma and milk.

A first of its kind, simple, rapid, and sensitive liquid chromatography mass spectrometry (LC-MS/MS) method was developed and validated for quantification of perindopril and perindoprilat in both human plasma and breast milk. The analytes and internal standards (phenazone and acetyl salicylic acid) were extracted from biological matrices by protein precipitation. A Phenomenex® C-18 column was used to provide an appropriate chromatographic separation of the analytes, followed by detection with tandem mass spectrometry. Gradient chromatographic and mass spectrometric detection conditions with mobile phases (A: 5% methanol + 0.1% formic acid in water v/v, and B: 95% methanol + 0.1% formic acid in water v/v) were developed to achieve a LOQ of 0.5 ng/mL in both human plasma and milk. The method was suitable of evaluating clinical samples. The mass transition was followed as m/z 369.10/172.00 for perindopril, m/z 339.00/168.10 for perindoprilat, m/z 188.90/55.95 for phenazone, and m/z 179.04/137.02 for acetyl salicylic acid. The developed method was optimized and validated with a linear range of 0.1-200 ng/mL (r 2 = better than 0.99 for both perindopril and perindoprilat). The precision and accuracy values were within 15% CV. The overall recovery of the analytes was 80-110%. The method has good specificity and repeatability. Stability studies were conducted in both human plasma and bovine milk for up to 3 months, at the storage conditions of 25, 4, and -80 °C.

A new LC-MS/MS bioanalytical method for atenolol in human plasma and milk.

AIM: A new sensitive LC-MS/MS method for the quantification of atenolol in human plasma and milk has been developed for clinical lactation studies. METHODS & RESULTS: Atenolol and the internal standard, phenazone, were extracted from biological matrices by protein precipitation. A Phenomenex® C-18 column and gradient chromatographic conditions were used for separation of the analyte, followed by detection with MS. Stability of samples was confirmed for atenolol in human plasma and milk for up to 3 months. Linearity range of 1-800 ng/ml (r2 = 0.9995), the precision within 15% CV and the recovery of the analyte (80-100% range) were achieved. CONCLUSION: A new validated analytical method for atenolol in plasma and milk was developed.

Audit of domperidone use as a galactogogue at an Australian tertiary teaching hospital.

BACKGROUND: Domperidone is often used to promote lactation among women who have difficulty breastfeeding. OBJECTIVE: To examine prescribing and dispensing practices of domperidone at the Women's and Children's Hospital (WCH), Adelaide. METHODS: A retrospective audit of domperidone dispensing among women with singleton pregnancies who delivered at the WCH between January 2000 and July 2010 was undertaken. Women dispensed domperidone were identified using WCH pharmacy dispensing records. Maternal and infant clinical data were obtained from the WCH Perinatal Statistics Collection. An audit of paper-based medical records was undertaken for a random sample of 261 mother-child pairs to collect prescribing and additional clinical data. RESULTS: From 2000 to 2010, 1605 women were dispensed domperidone. There was a steady increase in the percentage of women dispensed domperidone, from < 0.5% in 2000 to > 5% of total WCH pregnancies in 2010. Among women dispensed domperidone, the percentage of women who received > 1 dispensing remained consistent (20%) over time, as did the median number of days (12) from delivery to first dispensing. Multiparous women were more likely to receive domperidone within 3 days following delivery compared to primiparous women (8% vs 4%; P < .01). Most women (80%) received directions to take domperidone according to a standard tapering dosing regimen over 12 days. Notably, 60% of women had no documentation of being assessed by a lactation consultant. CONCLUSION: From 2000 to 2010, there was a considerable increase in domperidone dispensing. With a lack of clinical evidence to guide use, current practice appears to be based on anecdotal evidence.