BUCCAL ABSORPTION OF ETOMIDATE FROM A SOLID FORMULATION IN DOGS

Etomidate is typically administered IV for the induction of general an esthesia. We believe that oral transmucosal absorption may extend etom idate's use to premedication and conscious sedation. Our objective was to study the oral mucosal absorption kinetics and bioavailability of etomidate ina solid dose form in dogs. A solid dose form containing 50 mg of etomidate in sorbitol for buccal administration was prepared. E ach dog was administered both IV etomidate and buccal etomidate on sep arate days. Serum etomidate concentrations after IV administration wer e fit to a two-compartment pharmacokinetic model. The rates at which e tomidate enters the systemic circulation via buccal mucosal absorption were calculated from serum concentrations from mucosal and IV adminis trations using model-dependent constrained numerical deconvolution. Th e apparent permeability coefficient and bioavailability were also dete rmined. The mean (+/- SD) maximal serum etomidate concentration after buccal mucosal absorption from the 50-mg dose unit was 239 +/- 79 ng/m L. The time to reach maximal serum concentration was 12.5 +/- 1.8 min. Peak absorption rate of etomidate into the systemic circulation was 8 32 +/- 417 mu g/min For all dogs, 90% or more of the absorption via bu ccal mucosa took place during the period in which the drug was in cont act with the mucosa (15 min). The apparent transbuccal mucosal permeab ility coefficient was 9.1 +/- 4.2 x 10(-4) cm/s, higher than values of any other compounds examined. Bioavailability calculated using the ar ea under the serum etomidate concentration versus time curve method an d the deconvolution method was 13.6% +/- 10.7% and 16.6% +/- 7.6%, res pectively. In conclusion etomidate is highly permeable through the can ine buccal mucosa. Implications: Etomidate is highly permeable through the canine buccal mucose. Both the onset and the termination of bucca l mucosal absorption of etomidate are rapid, which suggests that titra table delivery of etomidate may be possible by buccal administration.