title: A review of the clinical pharmacokinetics of opioids, benzodiazepines, and antimigraine drugs delivered intranasally.
abstract: BACKGROUND
  Interest in the development of drug-delivery 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).
authors.affiliation: Department of Clinical Pharmacology, Maastricht University Medical Centre, Maastricht, the Netherlands. N.veldhorst@mumc.nl
authors.forename: Nicole M L
authors.initials: NM
authors.lastname: Veldhorst-Janssen
authors.forename: Audrey A A
authors.initials: AA
authors.lastname: Fiddelers
authors.forename: Paul-Hugo M
authors.initials: PH
authors.lastname: van der Kuy
authors.forename: Cees
authors.initials: C
authors.lastname: Neef
authors.forename: Marco A E
authors.initials: MA
authors.lastname: Marcus
mesh_terms: D000281:Administration, Intranasal; D000284:Administration, Oral; D000336:Aerosols; D001569:Benzodiazepines / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D001682:Biological Availability; D005260:Female; D006801:Humans; D007275:Injections, Intravenous; D008297:Male; D008881:Migraine Disorders / Q000188:drug therapy*; D009292:Narcotic Antagonists / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*
chemical_list: D000336:Aerosols; D009292:Narcotic Antagonists; D001569:Benzodiazepines