Oral transmucosal etomidate in volunteers

Area of Science:

• Pharmacology
• Drug Delivery Systems
• Clinical Pharmacology

Background:

• Oral transmucosal drug delivery is established for medications like fentanyl and midazolam.
• Etomidate's properties suggest suitability for transmucosal administration.
• Transmucosal etomidate could expand its use for sedation and anxiolysis.

Purpose of the Study:

• To evaluate the safety and efficacy of a novel oral transmucosal etomidate (OTET) dosage form in humans.
• To determine the pharmacokinetic profile of orally administered etomidate.
• To assess the dose-related effects of OTET on sedation and physiological parameters.

Main Methods:

• Ten healthy adults received single doses of 12.5, 25, 50, and 100 mg of OTET on separate days.
• Serum etomidate levels, sedation, respiratory and cardiovascular variables were monitored.
• Subjective assessments of taste and side effects were recorded.

Main Results:

• Etomidate was detected in blood within 5 minutes, with peak concentrations 20-30 minutes post-administration (61-174 ng/ml, dose-related).
• Dose-dependent drowsiness and light sleep occurred 10-20 minutes after administration, lasting 30-60 minutes.
• No significant adverse events like hypoxemia or hypotension were observed; nausea was rare, and taste was rated as unpleasant at higher doses.

Conclusions:

• Oral transmucosal etomidate (OTET) provides dose-related sedation and achieves significant serum concentrations with a favorable safety profile.
• The rapid onset and short duration of action suggest OTET's utility for procedures requiring brief, mild to moderate sedation.
• Further research and development of this novel etomidate dosage form are recommended.