Chemistry and Drug Metabolism, Intramural Research Program, National Institute on Drug Abuse, National Institutes of Health, Baltimore, Maryland 21224, USA.
J Anal Toxicol. 2010 Oct;34(8):498-505. doi: 10.1093/jat/34.8.498.
Buprenorphine is under investigation in the U.S. as pharmacotherapy for opioid-dependent pregnant women. Buprenorphine and metabolites were quantified in umbilical cord specimens from women receiving daily buprenorphine doses. Correlations between maternal buprenorphine dose, buprenorphine and metabolite umbilical cord concentrations, and neonatal outcomes were investigated, as well as the ability to identify heroin and cocaine relapse during pregnancy. Umbilical cord concentrations were compared to those of matched umbilical cord plasma and meconium. Buprenorphine metabolites were detected in all cords, but buprenorphine itself was absent. Concentration ranges were 1.2-5.1 ng/g norbuprenorphine, 1.7-4.2 ng/g buprenorphine-glucuronide, and 8.3-23 ng/g norbuprenorphine-glucuronide. Cord concentrations were similar to those in plasma, and lower (16-210-fold), although statistically correlated, than those in meconium. Significant positive correlations were observed for buprenorphine-glucuronide concentrations in umbilical cord and mean maternal BUP daily dose throughout pregnancy and third trimester, but buprenorphine biomarker concentrations did not predict neonatal outcomes. Opiate concentrations were lower (200-fold) in umbilical cord than in meconium, and when cocaine was present in meconium, it was not identified in cord. Umbilical cord can serve as an alternative matrix for identifying prenatal drug-exposure, but is much less sensitive than meconium. Buprenorphine provided a controlled drug administration model for evaluating drug disposition in the maternal-fetal dyad.
丁丙诺啡在美国被作为治疗阿片类药物依赖孕妇的药物治疗方法进行研究。对接受丁丙诺啡日剂量的孕妇的脐带标本进行了丁丙诺啡及其代谢物的定量分析。研究了母体丁丙诺啡剂量、丁丙诺啡及其代谢物脐带浓度与新生儿结局之间的相关性，以及在妊娠期间识别海洛因和可卡因复发的能力。将脐带浓度与匹配的脐带血浆和胎粪进行了比较。所有脐带中都检测到了丁丙诺啡代谢物，但未检测到丁丙诺啡本身。检测到的浓度范围为：1.2-5.1ng/g 去甲丁丙诺啡、1.7-4.2ng/g 丁丙诺啡-葡萄糖醛酸苷和 8.3-23ng/g 去甲丁丙诺啡-葡萄糖醛酸苷。脐带浓度与血浆相似，比胎粪（16-210 倍）低，尽管与胎粪具有统计学相关性。在整个孕期和孕晚期，均观察到丁丙诺啡-葡萄糖醛酸苷浓度与母体 BUP 日平均剂量之间存在显著正相关，但丁丙诺啡生物标志物浓度并不能预测新生儿结局。脐带中阿片类药物浓度（200 倍）比胎粪低，并且当可卡因存在于胎粪中时，在脐带中并未检出。脐带可以作为一种替代基质来识别产前药物暴露，但敏感性远低于胎粪。丁丙诺啡为评估母体-胎儿对子代药物处置提供了一个药物管理模型。
