Thomas Jefferson University, Philadelphia, Pennsylvania, USA.
Metrum Research Group, Tariffville, Connecticut, USA.
Clin Pharmacol Ther. 2018 Jun;103(6):1029-1037. doi: 10.1002/cpt.1064. Epub 2018 Apr 28.
Neonatal abstinence syndrome (NAS) is a condition affecting newborns that are exposed to an opioid in utero. In a randomized, controlled trial assessing the efficacy of buprenorphine and morphine in NAS, blood samples were analyzed from a subset of patients receiving buprenorphine along with NAS scores. The data were used to validate and adapt an existing model of buprenorphine in neonates and to identify relationships between buprenorphine or norbuprenorphine pharmacokinetics (PK) and efficacy or safety. The time to NAS stabilization was found to decrease with increasing buprenorphine exposure. This pharmacokinetic-pharmacodynamic (PK-PD) relationship was able to be quantified and adequately described with a mathematical model. The findings confirm a previous PK model of buprenorphine and extend the model to describe the PK of norbuprenorphine and to identify a novel PK-PD relationship of buprenorphine in NAS. This model will allow optimization of dosing strategies in future clinical trials.
新生儿戒断综合征（NAS）是一种影响暴露于子宫内阿片类药物的新生儿的病症。在一项评估丁丙诺啡和吗啡治疗 NAS 疗效的随机对照试验中，对接受丁丙诺啡治疗的亚组患者的血样进行了分析，并对 NAS 评分进行了分析。这些数据用于验证和调整新生儿丁丙诺啡的现有模型，并确定丁丙诺啡或去甲丁丙诺啡药代动力学（PK）与疗效或安全性之间的关系。结果发现，NAS 稳定化的时间随着丁丙诺啡暴露量的增加而减少。这种药代动力学-药效学（PK-PD）关系可以用数学模型进行定量和充分描述。这些发现证实了之前丁丙诺啡的 PK 模型，并扩展了该模型以描述去甲丁丙诺啡的 PK，并确定了丁丙诺啡在 NAS 中的新 PK-PD 关系。该模型将有助于优化未来临床试验中的剂量策略。
