Strang John, McDonald Rebecca, Tas Basak, Day Ed
National Addiction Centre, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.
Addiction. 2016 Apr;111(4):574-82. doi: 10.1111/add.13209. Epub 2016 Feb 3.
Take-home naloxone is increasingly provided to prevent heroin overdose deaths. Naloxone 0.4-2.0 mg is licensed for use by injection. Some clinicians supply improvised nasal naloxone kits (outside licensed approval). Is this acceptable?
(1) To consider provision of improvised nasal naloxone in clinical practice and (2) to search for evidence for pharmacokinetics and effectiveness (versus injection).
(1) To document existing nasal naloxone schemes and published evidence of pharmacokinetics (systematic search of the CINAHL, Cochrane, EMBASE and MEDLINE databases and 18 records included in narrative synthesis). (2) To analyse ongoing studies investigating nasal naloxone (WHO International Clinical Trials Registry Platform and US NIH RePORT databases).
(1) Multiple studies report overdose reversals following administration of improvised intranasal naloxone. (2) Overdose reversal after nasal naloxone is frequent but may not always occur. (3) Until late 2015, the only commercially available naloxone concentrations were 0.4 mg/ml and 2 mg/2 ml. Nasal medications are typically 0.05-0.25 ml of fluid per nostril. The only published study of pharmacokinetics and bioavailability finds that nasal naloxone has poor bioavailability. QUESTIONS FOR DEBATE: (1) Why are pharmacokinetics and bioavailability data for nasal naloxone not available before incorporation into standard clinical practice? (2) Does nasal naloxone have the potential to become a reliable clinical formulation? (3) What pre-clinical and clinical studies should precede utilization of novel naloxone formulations as standard emergency medications?
The addictions treatment field has rushed prematurely into the use of improvised nasal naloxone kits. Evidence of adequate bioavailability and acceptable pharmacokinetic curves are vital preliminary steps, especially when effective approved formulations exist.
越来越多地提供纳洛酮带回家以预防海洛因过量致死。0.4 - 2.0毫克的纳洛酮被批准用于注射。一些临床医生提供临时制作的鼻腔用纳洛酮试剂盒（未经批准许可）。这样做是否可以接受？
（1）考虑在临床实践中提供临时制作的鼻腔用纳洛酮，以及（2）寻找其药代动力学和有效性（与注射相比）的证据。
（1）记录现有的鼻腔用纳洛酮方案以及已发表的药代动力学证据（对CINAHL、Cochrane、EMBASE和MEDLINE数据库进行系统检索，并将18条记录纳入叙述性综述）。（2）分析正在进行的关于鼻腔用纳洛酮的研究（世界卫生组织国际临床试验注册平台和美国国立卫生研究院研究项目在线报告工具数据库）。
（1）多项研究报告了临时制作的鼻内用纳洛酮给药后过量中毒的逆转情况。（2）鼻腔用纳洛酮给药后过量中毒的逆转情况很常见，但并非总是会发生。（3）直到2015年末，唯一可商购的纳洛酮浓度为0.4毫克/毫升和2毫克/2毫升。鼻腔用药通常每侧鼻孔为0.05 - 0.25毫升液体。唯一一项已发表的关于药代动力学和生物利用度的研究发现鼻腔用纳洛酮的生物利用度较差。
（1）为什么在将鼻腔用纳洛酮纳入标准临床实践之前没有其药代动力学和生物利用度数据？（2）鼻腔用纳洛酮是否有潜力成为一种可靠的临床制剂？（3）在将新型纳洛酮制剂用作标准急救药物之前，应该进行哪些临床前和临床研究？
成瘾治疗领域过早地匆忙使用临时制作的鼻腔用纳洛酮试剂盒。充分的生物利用度证据和可接受的药代动力学曲线是至关重要的初步步骤，尤其是当存在有效的批准制剂时。
