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Epilepsia. 1998 Mar;39(3):290-4.

Buccal absorption of midazolam: pharmacokinetics and EEG pharmacodynamics.

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Institute of Child Health (UCLMS), London, UK.



To determine whether buccal/sublingual administration of midazolam (MDL) would lead to detectable venous concentrations and EEG changes in 10 healthy volunteers.


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.


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.


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.

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