ORAL TRANSMUCOSAL ETOMIDATE IN VOLUNTEERS

Background: The oral transmucosal route of delivery is now used for ma ny drugs, including fentanyl and midazolam. Etomidate's pharmacokineti c profile and physiochemical properties suggest it may be suitable for transmucosal delivery. Transmucosal delivery might extend etomidate's use to sedation and anxiolysis. This is the first study in humans to examine the oral transmucosal administration of a novel etomidate dosa ge form. Methods: Ten healthy adult volunteers consumed 12.5-mg, 25-mg , 50-mg, and 100-mg doses of oral transmucosal etomidate (OTET) on fou r different study days. Serum etomidate concentrations, sedation, resp iratory and cardiovascular variables, taste, and side effects were det ermined. Results: Five minutes after OTET administration, etomidate wa s detected in the venous blood, Mean peak concentrations occurred 20-3 0 min later and ranged from 61-174 ng/ml, related to the dose administ ered. Drowsiness and light sleep occurred in a dose-related manner 10- 20 min after administration and lasted for 30-60 min. No episodes of S p(O2) <90%, hypotension, or emesis occurred at any dose throughout the study. Nausea was rare. Two volunteers exhibited a brief episode of i nvoluntary tremor after the 100-mg dose. The bitter taste of OTET was judged increasingly unpleasant with escalating doses. Conclusions: Ora l transmucosal etomidate produces dose-related increases in sedation a nd clinically significant serum concentrations with minimal side effec ts. The time course of these effects suggests that OTET might be usefu l when brief mild to moderate sedation with rapid recovery is desirabl e. Further development of this novel dosage form is warranted.