Dale O, Hjortkjaer R, Kharasch E D
Department of Anesthesia and Medical Imaging, Norwegian University of Science and Technology, Trondheim, Norway.
Acta Anaesthesiol Scand. 2002 Aug;46(7):759-70. doi: 10.1034/j.1399-6576.2002.460702.x.
Nasal administration of opioids may be an alternative route to intravenous, subcutaneous, oral transmucosal, oral or rectal administration in some patients. Key features may be self-administration, combined with rapid onset of action. The aim of this paper is to evaluate the present base of knowledge on this topic.
The review is based on human studies found in Medline or in the reference list of these papers. The physiology of the nasal mucosa and some pharmaceutical aspects of nasal administration are described. The design of each study is described, but not systematically evaluated.
Pharmacokinetic studies in volunteers are reported for fentanyl, alfentanil, sufentanil, butorphanol, oxycodone and buprenorphine. Mean times for achieving maximum serum concentrations vary from 5 to 50 min, while mean figures for bioavailability vary from 46 to 71%. Fentanyl, pethidine and butorphanol have been studied for postoperative pain. Mean onset times vary from 12 to 22 min and times to peak effect from 24 to 60 min. There is considerable interindividual variation in pharmacokinetics and clinical outcome. This may partly be due to lack of optimization of nasal formulations. Patient-controlled nasal analgesia is an effective alternative to intravenous PCA. Adverse effects are mainly those related to the opioids themselves, rather than to nasal administration. Some experience with nasal opioids in outpatients and for chronic pain has also been reported.
Nasal administration of opioids has promising features, but is still in its infancy. Adequately designed clinical studies are needed. Improvements of nasal sprayer devices and opioid formulations may improve clinical outcome.
对于某些患者而言,经鼻给予阿片类药物可能是静脉、皮下、口腔黏膜、口服或直肠给药的替代途径。其主要特点可能是可自我给药,且起效迅速。本文旨在评估关于该主题的现有知识基础。
本综述基于在Medline或这些论文的参考文献列表中找到的人体研究。描述了鼻黏膜的生理学以及鼻内给药的一些药学方面。描述了每项研究的设计,但未进行系统评估。
报告了对芬太尼、阿芬太尼、舒芬太尼、布托啡诺、羟考酮和丁丙诺啡在志愿者中的药代动力学研究。达到最大血清浓度的平均时间为5至50分钟,而生物利用度的平均数值为46%至71%。已对芬太尼、哌替啶和布托啡诺用于术后疼痛进行了研究。平均起效时间为12至22分钟,达到峰值效应的时间为24至60分钟。药代动力学和临床结果存在相当大的个体差异。这可能部分归因于鼻用制剂缺乏优化。患者自控经鼻镇痛是静脉自控镇痛的有效替代方法。不良反应主要与阿片类药物本身有关,而非与经鼻给药有关。也报告了在门诊患者中使用鼻用阿片类药物以及用于慢性疼痛的一些经验。
经鼻给予阿片类药物具有良好的前景,但仍处于起步阶段。需要进行设计充分的临床研究。改进鼻喷雾器装置和阿片类药物制剂可能会改善临床效果。