Estimated infant exposure to enantiomer-specific methadone levels in breastmilk

Debra L. Bogen*, James M. Perel, Joseph C. Helsel, Barbara H. Hanusa, Matthew Thompson, Katherine L. Wisner

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

24 Scopus citations


Background and Objectives: Breastfeeding, a public health priority, improves outcomes for infants. Methadone is dispensed as a racemic mixture; R-methadone is the active enantiomer. Pharmacologic data for R-methadone in breastmilk could improve risk-benefit decision-making for treatment of lactating women. This study estimated infant exposure to R- and S-methadone via breastmilk by theoretic infant dose (TID) and relative infant dose (RID) and reported the milk-to-maternal plasma (M/P) ratio. Methods: Women treated with methadone doses of 40-200mg/day (mean, 102mg/day) provided concomitantly collected plasma and breastmilk samples 1-6 days after delivery. Most (16 of 20) samples were taken at the time of peak maternal plasma levels; thus infant exposure estimates are for maximum possible exposure. Concentrations of R- and S-methadone were measured in maternal plasma and breastmilk; M/P ratio, TID, and RID were calculated for each enantiomer and total methadone. Results: The 20 participants were 18-38 years old and publicly insured; a quarter did not complete high school, and only one was not white. R-Methadone concentration was 1.3-3.0 times that of S-methadone in all breastmilk samples. The mean (SD) R-, S-, and total methadone M/P ratios were 0.52 (0.28), 0.28 (0.15), and 0.40 (0.21), respectively. Mean (range) R-, S-, and total methadone TID were 0.02mg/kg/day (0.004-0.099), 0.013mg/kg/day (0.002-0.071), and 0.033mg/kg/day (0.006-0.170), respectively. Mean (range) RID of R-, S-, and total methadone were 2.7% (0.7-10.1%), 1.6% (0.3-7.2%), and 2.1% (0.52-8.8%), respectively. Conclusions: R-Methadone is found in higher concentrations than S-methadone in breastmilk. Even at high methadone doses, breastmilk methadone concentrations were relatively low and support American Academy of Pediatrics recommendations that dose should not be a factor in determining whether women on methadone breastfeed.

Original languageEnglish (US)
Pages (from-to)377-384
Number of pages8
JournalBreastfeeding Medicine
Issue number6
StatePublished - Dec 1 2011

ASJC Scopus subject areas

  • Pediatrics
  • Health Policy
  • Obstetrics and Gynecology
  • Maternity and Midwifery

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