Buccal absorption of midazolam: pharmacokinetics and EEG pharmacodynamics.
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.
Scott
R C
RC
Institute of Child Health (UCLMS), London, UK.
Besag
F M
FM
Boyd
S G
SG
Berry
D
D
Neville
B G
BG
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
D010919:Placebos; D008874:Midazolam