Shendre Aditi, Liu Xiaofu, Chiang ChienWei, Goodwin Andrew, Oteng Samuel-Richard, Deypalubos Jiezel A F, Zhang Shijun, Wang Lei, Liu Jianing, Abbasi Mohammad Yaseen, Aruldhas Blessed Winston, Zaidi Syed Saoud, Kirkpatrick Lindsey Marie, Silva Lais Da, Overholser Brian R, O'Kane Aislinn M, Kannankeril Prince J, Patrick Stephen W, Wiese Andrew D, Quinney Sara K, Li Lang
Department of Biomedical Informatics, College of Medicine, The Ohio State University Wexner Medical Center, Columbus, Ohio, USA.
Division of Clinical Pharmacology, Department of Medicine, IUSM, Indianapolis, Indiana, USA.
Pharmacotherapy. 2025 Jun;45(6):367-385. doi: 10.1002/phar.70024. Epub 2025 May 15.
The use and misuse of opioids has surged in the past decade, with nearly half of the users being female. Although opioid use is lower among pregnant women, trends mirror the general population. While pediatric exposures largely occur through prescriptions. This review presents a novel landscape analysis of pharmacology knowledge gaps in opioids in the maternal and pediatric populations. We queried PubMed for studies on 27 opioids, focusing on pharmacokinetics (PK), and pharmacoepidemiology (PE) or clinical trials (CT) in maternal and pediatric populations. English-language publications were included, and data were synthesized to identify gaps. Additionally, MarketScan claims data and United States Food and Drug Administration (FDA) drug labels were analyzed to compare scientific evidence, opioid prescriptions/orders, and FDA recommendations. Morphine, fentanyl, methadone, and buprenorphine are the most researched opioids in PK and PE/CT literature in both populations, but hydrocodone, oxycodone, and codeine are the most prescribed. Nine opioids lack FDA labels, and four of the 18 labeled drugs lack any human data. Hydrocodone, oxycodone, and codeine labels include lactation-focused PK information, with some pediatric clinical data for the latter two. Seven opioids lack PK and PE/CT studies in the maternal population, and PK research is absent for seven opioids, and PE/CT data is lacking for eight opioids in the pediatric population. PK studies often focus on labor, delivery, and lactation accompanied by neonatal data, whereas pregnancy research mainly occurs in PE studies. In pediatric populations, study types are evenly distributed among children, but PE studies focus more on adolescents. Drug concentration is the most reported parameter in PK studies, and neonatal opioid withdrawal syndrome (NOWS) is a key outcome in both PK and PE studies. NOWS is also researched more using real-world data, whereas neurodevelopmental outcomes are often captured in prospective observational studies. There is substantial disparity between the most commonly researched and prescribed opioids. In particular, the opioid pharmacology knowledge gaps are larger in pregnant women and for the highly prescribed opioids hydrocodone and oxycodone. The limited human data in FDA labels underscores the need for additional studies. Studies using real-world data can potentially help address these gaps.
在过去十年中，阿片类药物的使用和滥用情况激增，近一半的使用者为女性。尽管孕妇中的阿片类药物使用率较低，但其趋势与普通人群相似。儿科接触阿片类药物主要是通过处方。本综述对孕产妇和儿科人群阿片类药物的药理学知识空白进行了新颖的全景分析。我们在PubMed上检索了关于27种阿片类药物的研究，重点关注孕产妇和儿科人群的药代动力学（PK）、药物流行病学（PE）或临床试验（CT）。纳入英文出版物，并对数据进行综合分析以确定空白。此外，还分析了MarketScan索赔数据和美国食品药品监督管理局（FDA）的药品标签，以比较科学证据、阿片类药物处方/医嘱和FDA建议。吗啡、芬太尼、美沙酮和丁丙诺啡是这两个人群PK和PE/CT文献中研究最多的阿片类药物，但氢可酮、羟考酮和可待因的处方量最大。9种阿片类药物没有FDA标签，18种有标签的药物中有4种缺乏任何人体数据。氢可酮、羟考酮和可待因的标签包括以哺乳期为重点的PK信息，后两者有一些儿科临床数据。7种阿片类药物在孕产妇人群中缺乏PK和PE/CT研究，7种阿片类药物缺乏PK研究，8种阿片类药物在儿科人群中缺乏PE/CT数据。PK研究通常侧重于分娩、产时和哺乳期并伴有新生儿数据，而孕期研究主要出现在PE研究中。在儿科人群中，研究类型在儿童中分布均匀，但PE研究更多地关注青少年。药物浓度是PK研究中报道最多的参数，新生儿阿片类药物戒断综合征（NOWS）是PK和PE研究中的关键结局。NOWS也更多地使用真实世界数据进行研究，而神经发育结局通常在前瞻性观察研究中获得。最常研究的阿片类药物和处方量最大的阿片类药物之间存在很大差异。特别是，孕妇以及处方量很大的氢可酮和羟考酮的阿片类药物药理学知识空白更大。FDA标签中有限的人体数据凸显了进行更多研究的必要性。使用真实世界数据的研究可能有助于填补这些空白。
