Estimated Dose Exposure of the Neonate to Buprenorphine and Its Metabolite Norbuprenorphine via Breastmilk During Maternal Buprenorphine Substitution Treatment

Objective: The aim of the present study was to estimate the dose of buprenorphine and its primary metabolite norbuprenorphine that a breastfed infant would receive during maternal maintenance treatment with buprenorphine. Study Design: Seven pregnant opioid-dependent women taking buprenorphine (median, 7 mg/day; range, 2.4-24 mg) and who intended to breastfeed were recruited. After lactation was established, several milk samples were collected from each subject over a 24-hour dose interval, and buprenorphine and norbuprenorphine concentrations were measured by liquid chromatography-tandem mass spectrometry. The average concentration (C-avg) across the dose interval was estimated as for both buprenorphine and norbuprenorphine (as buprenorphine equivalents). Absolute infant dose (AID), defined as C-avg x daily milk intake, and relative infant dose (RID), defined as 100 x AID/weight-adjusted maternal daily dose, via milk were calculated, assuming a milk intake of 0.15 L/kg/day. The infant's health and progress were assessed directly and by questionnaire on the study day. Results: Mean (95% confidence interval) norbuprenorphine concentration in milk and AID values (1.94 [0.79-3.08] mu g/L and 0.29 [0.12-0.46] mu g/kg/day, respectively) were approximately half those for buprenorphine (3.65[1.61-5.7] mu g/L and 0.55 [0.24-0.85] mu g/kg/day, respectively). Similarly, the mean RID values were 0.18% (0.11-0.25%) for norbuprenorphine and 0.38% (0.23-0.53%) for buprenorphine. The breastfed infants showed no adverse effects, were all in good health, and were progressing as expected. Conclusion: Thus the dose of buprenorphine and norbuprenorphine received via milk is unlikely to cause any acute adverse effects in the breastfed infant.