A review of the clinical pharmacokinetics of opioids, benzodiazepines, and antimigraine drugs delivered intranasally

详细信息    查看全文

• 作者：Nicole M.L. Veldhorst-Janssen ; Audrey A.A. Fiddelers ; Paul-Hugo M. van der Kuy ; Cees Neef ; Marco A.E. Marcus
• 关键词：systematic review ; nasal drug delivery ; pharmacokinetics ; opioids ; benzodiazepines ; antimigraine drugs
• 刊名：Clinical Therapeutics
• 出版年：2009
• 出版时间：December 2009
• 年：2009
• 卷：31
• 期：12
• 页码：2954-2987
• 全文大小：237 K

文摘

Background: Interest in the development of drugdelivery devices that might improve treatment compliance is growing. A dosage formulation that is easy to use, such as intranasal application with transmucosal absorption, may offer advantages compared with other routes of drug delivery. The literature concerning intranasal application is diffuse, with a large number of published studies on this topic. Some cerebroactive pharmaceuticals delivered intranasally might follow the pathway from the nose to the systemic circulation to the brain. To determine the suitability of these drugs for intranasal drug delivery, a systematic review was performed.

Objective: The aim of this review was to compare the pharmacokinetic properties of intranasal, intravenous, and oral formulations in 3 classes of cerebroactive drugs that might be suitable for intranasal delivery—opioids, benzodiazepines, and antimigraine agents.

Methods: A search of MEDLINE, PubMed, Cumulative Index of Nursing and Allied Health Literature, EMBASE, and Cochrane Database of Systematic Reviews (dates: 1964–April 2009) was conducted for pharmacokinetic studies of drugs that might be suitable for intranasal delivery. A comparison of pharmacokinetic data was made between these 3 routes of administration.

Results: A total of 45 studies were included in this review. Most of the opioids formulated as an intranasal spray reached a T_max within 25 minutes. The bioavailability of intranasal opioids was high; in general, >50 % compared with opioids administered intravenously. Intranasal benzodiazepines had an overall T_max that varied from 10 to 25 minutes, and bioavailability was between 38 % and 98 % . T_max for most intranasal antimigraine drugs varied from 25 to 90 minutes. Intranasal bioavailability varied from 5 % to 40 % .

Conclusions: This review found that intranasal administration of all 3 classes of drugs was suitable for indications of rapid delivery, and that the pharmacokinetic properties differed between the intranasal, oral, and intravenous formulations (intravenous > intranasal > oral).