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Buccal Absorption of Midazolam: Pharmacokinetics and EEG Pharmacodynamics
Author(s) -
Scott Rod C.,
Besag Frank M. C.,
Boyd Stewart G.,
Berry David,
Neville Brian G. R.
Publication year - 1998
Publication title -
epilepsia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.687
H-Index - 191
eISSN - 1528-1167
pISSN - 0013-9580
DOI - 10.1111/j.1528-1157.1998.tb01375.x
Subject(s) - midazolam , buccal administration , anesthesia , pharmacokinetics , placebo , medicine , electroencephalography , pharmacodynamics , pharmacology , sedation , alternative medicine , pathology , psychiatry
Summary:Purpose: 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 ≤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.