Maternal Buprenorphine Dose Placenta Buprenorphine and Metabolite Concentrations and Neonatal Outcomes

摘要

Buprenorphine is approved as pharmacotherapy for opioid dependence in non-pregnant patients in multiple countries, and is currently under investigation for pregnant women in the US and Europe. This research evaluates the disposition of buprenorphine, opiates, cocaine, and metabolites in 5 term placentas from a US cohort. Placenta and matched meconium concentrations were compared, and relationships between maternal buprenorphine dose, placenta concentrations, and neonatal outcomes following controlled administration during gestation were investigated. Buprenorphine and/or metabolites were detected in all placenta specimens and were uniformly distributed across this tissue (CV<27.5%, 4 locations), except for buprenorphine in 3 placentas. In 2 of these, buprenorphine was not detected in some locations and, in the 3^rd placenta, was totally absent. Median (range) concentrations were buprenorphine 1.6ng/g (not detected to 3.2), norbuprenorphine 14.9ng/g (6.2 to 24.2), buprenorphine-glucuronide 3ng/g (1.3 to 5.0) and norbuprenorphine-glucuronide 14.7ng/g (11.4 to 25.8). Placenta is a potential alternative matrix for detecting in utero buprenorphine exposure, but at lower concentrations (15–70 fold) than in meconium. Statistically significant correlations were observed for mean maternal daily dose from enrollment to delivery and placenta buprenorphine-glucuronide concentration, and for norbuprenorphine-glucuronide concentrations and time to neonatal abstinence syndrome (NAS) onset and duration, and for norbuprenorphineorbuprenorphine-glucuronide ratio and maximum NAS score, and newborn length. Analysis of buprenorphine and metabolites in this alternative matrix, an abundant waste product available at the time of delivery, may be valuable for prediction of neonatal outcomes for clinicians treating newborns of buprenorphine-exposed women.