Pharmacokinetics and Breast Milk Transfer to Infants of Subcutaneous Extended-Release Buprenorphine for the Treatment of Individuals with Opioid Use Disorder.

Background: Extended-release buprenorphine (XR BUP) is commonly used for individuals with opioid-use disorder (OUD), however, with limited experience in pregnancy. N-methyl-2-pyrrolidone (NMP), an excipient of monthly XR BUP formulations, is a developmental toxicant. No information is available on pharmacokinetics or breast milk transfer in lactating individuals receiving XR BUP. Methods: Samples of maternal plasma, infant plasma, and breast milk were collected from lactating individuals between 0 and 6 months postpartum receiving monthly XR BUP. All samples were analyzed for BUP and NMP concentrations using a validated liquid chromatography-tandem mass spectrometry assay. Results: Three lactating individuals provided a total of nine maternal plasma, six infant plasma, and five breast milk samples. Mean BUP concentrations were 6.0 ng/mL (standard deviation [SD] 1.6) in maternal plasma, 8.9 ng/mL (SD 6.6) in breast milk, and below the lower limit of quantitation for all infant plasma samples. We estimated the relative infant dose (RID) of BUP to be 1%. NMP was detectable in maternal plasma (mean 5.43 μg/mL, SD 4.56) and breast milk (mean 3.83 μg/mL, SD 5.07) only from samples measured between 1 and 5 hours after dosing. NMP was not detected in infant plasma. Conclusions: Among lactating individuals receiving XR BUP, BUP was present in low levels in maternal plasma (similar to nonlactating individuals on XR BUP) and breast milk of lactating individuals receiving XR BUP (similar to lactating individuals on sublingual BUP), resulting in a low RID. NMP passes into breast milk, however, was not present in infant plasma. Additional data are needed before definitive conclusions can be made.