title: Buccal absorption of midazolam: pharmacokinetics and EEG pharmacodynamics.
abstract: OBJECTIVE
  To determine whether buccal/sublingual administration of midazolam (MDL) would lead to detectable venous concentrations and EEG changes in 10 healthy volunteers.
  
  
  METHODS
  The study consisted of an open-label and a double-blind phases. Subjects held 10 mg MDL in 2 ml peppermint-flavored fluid or peppermint-flavored placebo in their mouth for 5 min and then spat it out. Cardiorespiratory and EEG monitoring was performed in all subjects.
  
  
  RESULTS
  Venous MDL concentrations measured on 10 occasions from 5 to 600 min after administration showed a rapid increase for the first 20-30 min. However, changes in the 8- to 30-Hz frequencies identified by spectral analysis of the EEG showed changes in < or = 5-10 min in test but not in control subjects--more rapid than were expected from the venous absorption data. There were no significant adverse effects.
  
  
  CONCLUSIONS
  Our data provide direct evidence of the speed of cerebral effect of a drug. Our results suggest that the buccal/sublingual route of administration should be tested in emergency treatment of seizures as an alternative to the rectal route, over which it has clear practical advantages.
authors.affiliation: Institute of Child Health (UCLMS), London, UK.
authors.forename: R C
authors.initials: RC
authors.lastname: Scott
authors.forename: F M
authors.initials: FM
authors.lastname: Besag
authors.forename: S G
authors.initials: SG
authors.lastname: Boyd
authors.forename: D
authors.initials: D
authors.lastname: Berry
authors.forename: B G
authors.initials: BG
authors.lastname: Neville
mesh_terms: D000042:Absorption; D000278:Administration, Buccal; D000286:Administration, Sublingual; D000328:Adult; D004311:Double-Blind Method; D004569:Electroencephalography / Q000187:drug effects*; D006801:Humans; D008874:Midazolam / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000494:pharmacology*; D008991:Monitoring, Physiologic; D010919:Placebos; D013226:Status Epilepticus / Q000188:drug therapy
chemical_list: D010919:Placebos; D008874:Midazolam