Buprenorphine is approved as
pharmacotherapy for
opioid dependence in nonpregnant patients in multiple countries and is currently under investigation for pregnant women in the United States and Europe. This research evaluates the disposition of
buprenorphine,
opiates,
cocaine, and metabolites in five term placentas from a US cohort. Placenta and matched meconium concentrations were compared, and relationships among maternal
buprenorphine dose, placenta concentrations, and neonatal outcomes after controlled administration during gestation were investigated.
Buprenorphine and/or metabolites were detected in all placenta specimens and were uniformly distributed across this tissue (coefficient of variation less than 27.5%, four locations), except for
buprenorphine in three placentas. In two of these,
buprenorphine was not detected in some locations and in the third placenta was totally absent. Median (range) concentrations were 1.6 ng/g
buprenorphine (not detected to 3.2), 14.9 ng/g
norbuprenorphine (6.2-24.2), 3 ng/g
buprenorphine-
glucuronide (1.3-5.0), and 14.7 ng/g
norbuprenorphine-
glucuronide (11.4-25.8). Placenta is a potential alternative matrix for detecting in utero
buprenorphine exposure, but at lower concentrations (15- to 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 onset and duration, for
norbuprenorphine/
norbuprenorphine-
glucuronide ratio and maximum
neonatal abstinence syndrome 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.