Chemical and Drug Metabolism Section, National Institute on Drug Abuse, National Institutes of Health, Baltimore, Maryland, USA.
Ther Drug Monit. 2011 Aug;33(4):443-52. doi: 10.1097/FTD.0b013e31822724f0.
The purpose was to explore methadone and 2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine (EDDP) umbilical cord disposition, correlate with maternal methadone dose and neonatal outcomes, and evaluate the window of drug detection in umbilical cord of in utero illicit drug exposure.
Subjects comprised 19 opioid-dependent pregnant women from 2 clinical studies, one comparing methadone and buprenorphine pharmacotherapy for opioid-dependence treatment and the second examining monetary reinforcement schedules to maintain drug abstinence. Correlations were calculated for methadone and EDDP umbilical cord concentrations and maternal methadone dose, and neonatal outcomes. Cocaine- and opiate-positive umbilical cord concentrations were compared with those in placenta and meconium, and urine specimens collected throughout gestation.
Significant positive correlations were found for umbilical cord methadone concentrations and methadone mean daily dose, mean dose during the third trimester, and methadone cumulative daily dose. Umbilical cord EDDP concentrations and EDDP/methadone concentration ratios were positively correlated to newborn length, peak neonatal abstinence syndrome (NAS) score, and time-to-peak NAS score. Methadone concentrations and EDDP/methadone ratios in umbilical cord and placenta were positively correlated. Meconium identified many more cocaine- and opiate-positive specimens than did umbilical cord.
Umbilical cord methadone concentrations were correlated to methadone doses. Also, our results indicate that methadone and EDDP concentrations might help to predict the NAS severity. Meconium proved to be more suitable than umbilical cord to detect in utero exposure to cocaine and opiates; however, umbilical cord could be useful when meconium is unavailable due to in utero or delayed expulsion.
本研究旨在探讨美沙酮和 2-乙基-1,5-二甲基-3,3-二苯基吡咯烷（EDDP）脐血分布情况，及其与母体美沙酮剂量和新生儿结局的相关性，并评估药物检测窗口在胎儿接触非法药物的脐血中的应用。
研究对象为来自两项临床研究的 19 名阿片类药物依赖孕妇，其中一项比较了美沙酮和丁丙诺啡治疗阿片类药物依赖的药物治疗效果，另一项则研究了金钱强化维持药物禁欲方案。对脐带中美沙酮和 EDDP 浓度与母体美沙酮剂量及新生儿结局进行相关性分析。比较了脐带中可卡因和阿片阳性样本与胎盘和胎便中的浓度，并与整个孕期收集的尿液标本进行比较。
脐带中美沙酮浓度与美沙酮平均日剂量、孕晚期平均剂量和累积日剂量呈显著正相关。脐带 EDDP 浓度和 EDDP/美沙酮浓度比值与新生儿长度、新生儿戒断症状（NAS）评分峰值和 NAS 评分达峰时间呈正相关。脐带和胎盘中美沙酮浓度和 EDDP/美沙酮比值呈正相关。胎便中鉴定出更多可卡因和阿片阳性样本，而脐带中的阳性样本则较少。
脐带中美沙酮浓度与美沙酮剂量呈正相关。此外，我们的结果表明，美沙酮和 EDDP 浓度可能有助于预测 NAS 的严重程度。胎便比脐带更适合检测胎儿可卡因和阿片类药物暴露情况；然而，当胎便无法获得时，脐带可能是有用的。
