...
  • 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Pain medicine : >Pharmacokinetics and Abuse Potential of Asalhydromorphone, a Novel Prodrug of Hydromorphone, After Intranasal Administration in Recreational Drug Users
【24h】

Pharmacokinetics and Abuse Potential of Asalhydromorphone, a Novel Prodrug of Hydromorphone, After Intranasal Administration in Recreational Drug Users

机译：娱乐药物鼻内给药后，嗜含量的氢氨基甲肾小球酮的药代动力学和滥用潜力

获取原文
获取原文并翻译 | 示例
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

Objectives. Hydromorphone (HM) is a potent mu-opioid receptor agonist with high susceptibility for abuse. A prodrug of hydromorphone, asalhydromorphone (ASAL-HM), has been designed to deter nonoral forms of abuse associated with hydromorphone. This study evaluated the intranasal (IN) pharmacokinetics and exploratory abuse potential of ASAL-HM compared with HM. Design. Single-center, randomized, double-blind, crossover study. Setting. Clinical research site. Subjects. Healthy adult, nondependent recreational opioid users. Methods. Subjects (N =26) were randomized to receive IN administration of 16.1 mg of ASAL-HM and 8.0 mg of HM (molar-equivalent with respect to hydromorphone). Blood samples were taken through 24 hours postdose, and pharmacodynamic end points (Drug Liking, Feeling High, Take Drug Again, Overall Drug Liking) were assessed through eight hours postdose. Nasal irritation and safety were also assessed. Results. Relative to IN HM, the rate (C-max) and extent (area under the curve [AUC(0-last), AUC(0-inf)]) of exposure to hydromorphone following IN ASAL-HM were reduced by >= 50%. Consistent with these findings, scores on "at-the-moment" (i.e., Drug Liking E-max, High E-max) ) and retrospective (i.e., Take Drug Again, Overall Drug Liking) end points were statistically significantly lower for IN ASAL-HM, with mean/median differences ranging from 11.4 to 25.0 points. ASAL-HM produced greater nasal-related effects, such as nasal burning and facial pain, and a lower incidence of typical opioid-related adverse events such as euphoria, pruritus, and somnolence. Conclusions. The novel hydromorphone prodrug ASAL-HM produced marked reductions in hydromorphone exposure and abuse-related effects following IN administration compared with HM. ASAL-HM has desirable molecular features for incorporation into putative abuse-deterrent immediate-release and extended-release hydromorphone products.
机译：目标。氢磷（HM）是一种有效的MU-阿片受体激动剂，滥用易感性。已经设计成妨碍与氢酮相关的非侵害形式的氢氯酰胺（AsalHydromorphon（Asal-HM）。该研究评估了与HM相比，ASAL-HM的鼻内（IN）药代动力学和探索性滥用潜力。设计。单中心，随机，双盲，交叉研究。环境。临床研究现场。主题。健康成人，无依赖休闲阿片类药物。方法。受试者（n = 26）被随机化以获得16.1mg ASAl-HM和8.0mg的HM（相对于氢甲酰上的摩尔当量）。血液样品染色24小时，并通过八小时举行评估药物动力学终点（药物喜动性，感觉高，整体吸毒）进行评估。还评估了鼻刺激和安全性。结果。相对于HM，速率（C-MAX）和程度（曲线下的区域[AUC（0-最后），AUC（0-INF）]的暴露于ASAl-HM的氢酮（AUC（0-INF）]）减少> = 50 ％。与这些发现一致，评分“在当时的”（即，吸毒，高E-MAX））和回顾性（即，再次服用药物，整体药物喜欢）终点在统计学上显着降低ASAL-HM，平均/中位差异从11.4到25.0分。 ASAL-HM产生了更大的鼻腔相关效果，例如鼻腔燃烧和面部疼痛，以及典型的阿片类药物相关不良事件的发病率降低，如兴奋，瘙痒和嗜睡。结论。新型氢磷酮前药ASAL-HM在与HM相比，在给药中施用氢磷暴露和滥用相关的效果的标记降低。 ASAL-HM具有理想的分子特征，用于掺入推定的滥用滥用矛盾立即释放和延长释放的氢载体产物。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号