Original ArticleMaternal Buprenorphine Dose, Placenta Buprenorphine, and Metabolite Concentrations and Neonatal OutcomesConcheiro, Marta PhD*; Jones, Hendreé E PhD†; Johnson, Rolley E PharmD†‡; Choo, Robin PhD§; Shakleya, Diaa M PhD*; Huestis, Marilyn A PhD*Author Information From the *Chemistry and Drug Metabolism, Intramural Research Program, National Institute on Drug Abuse, National Institutes of Health, Baltimore, MD; †Department of Psychiatry and Behavioral Sciences' Johns Hopkins University School of Medicine, Baltimore, MD; ‡Reckitt Benckiser Pharmaceuticals, Inc., Richmond, VA; and §Department of Biology, University of Pittsburgh, Titusville, PA. Received for publication November 10, 2009; accepted December 21, 2009. This research was supported by the Intramural Research Program of the National Institute on Drug Abuse (NIDA), National Institutes of Health (NIH), and NIDA grant RO1 DA12220. Correspondence: Marilyn A. Huestis, PhD, Biomedical Research Center (BRC), 251 Bayview Boulevard, Suite 200, Room 05A721, Baltimore, MD 21224 (e-mail: firstname.lastname@example.org). Therapeutic Drug Monitoring: April 2010 - Volume 32 - Issue 2 - p 206-215 doi: 10.1097/FTD.0b013e3181d0bd68 Buy Metrics Abstract 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. © 2010 Lippincott Williams & Wilkins, Inc.