Wiegand Samantha L, Swortwood Madeleine J, Huestis Marilyn A, Thorp John, Jones Hendreé E, Vora Neeta L
Department of Obstetrics and Gynecology, University of North Carolina School of Medicine, Chapel Hill, North Carolina.
Department of Chemistry and Drug Metabolism, Intramural Research Program, National Institute on Drug Abuse National Institutes of Health, Baltimore, Maryland.
AJP Rep. 2016 Oct;6(4):e385-e390. doi: 10.1055/s-0036-1593993.
To quantify naloxone and metabolite concentrations in newborns prenatally exposed to sublingual buprenorphine/naloxone and to correlate neonatal and maternal metabolite concentrations. This is a prospective observational cohort study. Eleven pregnant women treated for opioid use disorder with sublingual buprenorphine/naloxone were enrolled. Maternal and newborn blood was collected and analyzed for naloxone, buprenorphine, and metabolites via liquid chromatography tandem mass spectrometry. Descriptive statistics and correlation coefficients were utilized to analyze data. Maternal daily naloxone and buprenorphine doses were 1 to 5 mg and 4 to 20 mg, respectively; the mean (standard deviation) time from medication until delivery was 9.9 (4.3) hours. Naloxone was below the limits of quantification (LOQ) in five infants and six mothers with a range of less than LOQ to 0.3 μg/L. There was a strong positive correlation between maternal and newborn naloxone concentrations: Spearman's ρ = 0.89 ( < 0.01). There were strong positive correlations between maternal and neonatal assays for the buprenorphine analyte concentrations: buprenorphine ρ = 0.88 ( < 0.01), norbuprenorphine ρ = 0.71 ( = 0.01), and norbuprenorphine-glucuronide ρ = 0.98 ( < 0.01), but not for buprenorphine-glucuronide, ρ = 0.53 ( = 0.10). Naloxone and buprenorphine are transferred to the fetus during prenatal exposure to maternal sublingual buprenorphine/naloxone. The quantity of naloxone transferred from maternal circulation is minimal and highly correlated with maternal concentrations.
量化产前暴露于舌下丁丙诺啡/纳洛酮的新生儿体内纳洛酮和代谢物浓度，并关联新生儿和母体代谢物浓度。 这是一项前瞻性观察队列研究。招募了11名接受舌下丁丙诺啡/纳洛酮治疗阿片类药物使用障碍的孕妇。采集母体和新生儿血液，通过液相色谱串联质谱法分析纳洛酮、丁丙诺啡和代谢物。使用描述性统计和相关系数分析数据。 母体每日纳洛酮和丁丙诺啡剂量分别为1至5毫克和4至20毫克；从用药到分娩的平均（标准差）时间为9.9（±4.3）小时。5名婴儿和6名母亲的纳洛酮低于定量限（LOQ），范围小于LOQ至0.3μg/L。母体和新生儿纳洛酮浓度之间存在强正相关：Spearman's ρ = 0.89（P < 0.01）。母体和新生儿丁丙诺啡分析物浓度检测之间存在强正相关：丁丙诺啡ρ = 0.88（P < 0.01），去甲丁丙诺啡ρ = 0.71（P = 0.01），去甲丁丙诺啡-葡萄糖醛酸苷ρ = 0.98（P < 0.01），但丁丙诺啡-葡萄糖醛酸苷除外，ρ = 0.53（P = 0.10）。 产前母体暴露于舌下丁丙诺啡/纳洛酮时，纳洛酮和丁丙诺啡会转移至胎儿体内。从母体循环转移的纳洛酮量极少，且与母体浓度高度相关。
