Division of Clinical Pharmacology, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA.
Department of Biomedical Sciences, University of South Carolina School of Medicine Greenville, Greenville, South Carolina, USA.
J Clin Pharmacol. 2021 Jul;61(7):857-870. doi: 10.1002/jcph.1811. Epub 2021 Feb 1.
Chronic intrauterine exposure to psychoactive drugs often results in neonatal opioid withdrawal syndrome (NOWS). When nonpharmacologic measures are insufficient in controlling NOWS, morphine, methadone, and buprenorphine are first-line medications commonly used to treat infants with NOWS because of in utero exposure to opioids. Research suggests that buprenorphine may be the leading drug therapy used to treat NOWS when compared with morphine and methadone. Currently, there are no consensus or standardized treatment guidelines for medications prescribed for NOWS. Opioids used to treat NOWS exhibit large interpatient variability in pharmacokinetics (PK) and pharmacodynamic (PD) response in neonates. Organ systems undergo rapid maturation after birth that may alter drug disposition and exposure for any given dose during development. Data regarding the PK and PD of opioids in neonates are sparse. Pharmacometric methods such as physiologically based pharmacokinetic and population pharmacokinetic modeling can be used to explore factors predictive of some of the variability associated with the PK/PD of opioids in newborns. This review discusses the utility of pharmacometric techniques for enhancing precision dosing in infants requiring opioid treatment for NOWS. Applying these approaches may contribute to optimizing the outcome by reducing cumulative drug exposure, mitigating adverse drug effects, and reducing the burden of NOWS in neonates.
慢性宫内接触精神活性药物通常会导致新生儿阿片类戒断综合征（NOWS）。当非药物措施不足以控制 NOWS 时，由于胎儿暴露于阿片类药物，吗啡、美沙酮和丁丙诺啡通常是用于治疗 NOWS 婴儿的一线药物。研究表明，与吗啡和美沙酮相比，丁丙诺啡可能是治疗 NOWS 的主要药物治疗方法。目前，对于治疗 NOWS 开具的药物，尚无共识或标准化治疗指南。用于治疗 NOWS 的阿片类药物在新生儿中的药代动力学（PK）和药效动力学（PD）反应存在很大的个体间差异。出生后，各个器官系统迅速成熟，这可能会改变任何特定剂量在发育过程中的药物分布和暴露。关于阿片类药物在新生儿中的 PK 和 PD 的数据很少。生理基于 PK 和群体 PK 建模等药效计量学方法可用于探索与新生儿阿片类药物 PK/PD 相关的一些可预测因素的差异。这篇综述讨论了药效计量学技术在增强需要治疗 NOWS 的婴儿的阿片类药物精确剂量方面的作用。应用这些方法可能有助于通过减少累积药物暴露、减轻药物不良反应和减少新生儿 NOWS 的负担来优化结果。
