无乙醇、舌下含服新生儿丁丙诺啡制剂 CHF6563 的生物利用度:在成人中开展的一项衔接研究。

Q2 Medicine
Walter K Kraft, Irene Barneschi, Maria Bocchi, Debora Santoro, Massimo Cella
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引用次数: 0

摘要

目的:舌下含服丁丙诺啡治疗新生儿阿片类药物戒断综合征(NOWS)的疗效已得到证实,但目前临床上使用的配方含有 30% 的乙醇。乙醇作为一种具有药理活性的辅料,最好从新生儿制剂中去除。本研究的目的是在健康成人中进行一项 I 期、开放标签、2 期、单剂量、交叉研究,以确定新型无乙醇制剂(CHF6563)与常用乙醇溶液相比的相对生物利用度:方法:18 名未服用过阿片类药物的成年志愿者在随机交叉治疗中服用了其中一种制剂。经过 10 天的清洗期后,受试者接受另一种制剂。在 48 小时内连续抽取血样进行药代动力学分析:与参考乙醇制剂相比,无乙醇丁丙诺啡溶液的 AUC0-last几何平均比值(90% CIs)为 0.80(0.65-0.99),Cmax 为 0.81(0.66-0.99)。与含乙醇的参比制剂相比,无乙醇制剂的受试者间变异性更大(AUC0-last的变异系数分别为59%和31.5%):在成年人群中,与乙醇溶液相比,含有广泛使用的辅料的丁丙诺啡新型无乙醇制剂的生物利用度略有下降。这些结果将为寻求开发无乙醇儿科药物制剂的人员提供参考。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
The Bioavailability of CHF6563, an Ethanol-Free, Sublingual Neonatal Buprenorphine Formulation: A Bridging Study Conducted in Adults.

Objective: Sublingual buprenorphine has demonstrated efficacy for treatment of the neonatal opioid withdrawal syndrome (NOWS), but the current formulation used in clinical practice contains 30% ethanol. Ethanol as a pharmacologically active excipient ideally should be removed from neonatal formulations. The objective of this study was to determine the relative bioavailability of a novel ethanol-free -formulation (CHF6563) compared with the commonly used ethanolic solution in a phase I, open-label, 2-period, -single-dose, crossover study in healthy adults.

Methods: Eighteen adult opioid-naïve volunteers were administered one of the formulations in a randomized crossover treatment. After a 10-day washout period, subjects received the other formulation. Serial blood samples were drawn for pharmacokinetic analysis over 48 hours.

Results: The geometric mean ratio (90% CIs) of the ethanol-free buprenorphine solution AUC0-last was 0.80 (0.65-0.99) and Cmax was 0.81 (0.66-0.99) compared with reference ethanolic formulation. The -ethanol-free formulation had a greater degree of intersubject variability than the ethanol-containing -reference formulation (coefficient of variation of 59% vs 31.5%, respectively, for AUC0-last).

Conclusions: In an adult population, a novel ethanol-free formulation of buprenorphine containing widely used excipients demonstrated a slight decrease in bioavailability when compared with an ethanolic solution. These results will inform those seeking to develop ethanol-free pediatric drug formulations.

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来源期刊
Journal of Pediatric Pharmacology and Therapeutics
Journal of Pediatric Pharmacology and Therapeutics Medicine-Pediatrics, Perinatology and Child Health
CiteScore
2.40
自引率
0.00%
发文量
90
期刊介绍: The Journal of Pediatric Pharmacology and Therapeutics is the official journal of the Pediatric Pharmacy Advocacy Group. JPPT is a peer-reviewed multi disciplinary journal that is devoted to promoting the safe and effective use of medications in infants and children. To this end, the journal publishes practical information for all practitioners who provide care to pediatric patients. Each issue includes review articles, original clinical investigations, case reports, editorials, and other information relevant to pediatric medication therapy. The Journal focuses all work on issues related to the practice of pediatric pharmacology and therapeutics. The scope of content includes pharmacotherapy, extemporaneous compounding, dosing, methods of medication administration, medication error prevention, and legislative issues. The Journal will contain original research, review articles, short subjects, case reports, clinical investigations, editorials, and news from such organizations as the Pediatric Pharmacy Advocacy Group, the FDA, the American Academy of Pediatrics, the American Society of Health-System Pharmacists, and so on.
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