BUCCAL ABSORPTION OF MIDAZOLAM - PHARMACOKINETICS AND EEG PHARMACODYNAMICS

Purpose: To determine whether buccal/sublingual administration of mida zolam (MDL) would lead to detectable venous concentrations and EEG cha nges 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 pepp ermint- flavored fluid or peppermint-flavored placebo in their mouth f or 5 min and then spat it out. Cardiorespiratory and EEC monitoring wa s performed in all subjects. Results: Venous MDL concentrations measur ed on 10 occasions from 5 to 600 min after administration showed a rap id increase for the first 20-30 min. However, changes in the 8- to 30- Hz frequencies identified by spectral analysis of the EEG showed chang es in less than or equal to 5-10 min in test but not in control subjec ts - more rapid than were expected from the venous absorption data. Th ere were no significant adverse effects. Conclusions: Out-data provide direct evidence of the speed of cerebral effect of a drug. Our result s suggest that the buccal/ sublingual route of administration should b e tested in emergency treatment of seizures as an alternative to the r ectal route, over which it has clear practical advantages.