Comparison of plasma benzodiazepine concentrations following intranasal and intravenous administration of diazepam to dogs

Objective- To determine whether plasma concentrations of benzodiazepines (B DZ) in dogs following intranasal (IN) administration of diazepam are compar able to concentrations following IV administration. Animals-6 (4 male, 2 female) healthy adult Greyhounds. Procedure-Dogs were randomly assigned to 2 groups of 3 dogs in a crossover design. Diazepam (0.5 mg/kg of body weight) was administered intravenously to dogs in group 1 and intranasally to dogs in group 2. Blood was collected from the jugular vein of each dog into tubes containing lithium heparin be fore and 3, 6, 9, 12, 15, 20, 30, 60, 120, 240, and 480 minutes following d iazepam administration. After a 4-day washout period, dogs in group 1 recei ved diazepam intranasally, dogs in group 2 received diazepam intravenously, and blood was again collected. Plasma concentration of BDZ was determined by use of a fluorescence polarization immunoassay. Results-Mean (+/- SD) peak plasma concentration of BDZ following IV adminis tration (1316 +/- 216 mu g/L) was greater than that following IN administra tion (448 +/- 41 mu g/L). Time to peak concentration was less than or equal to 3 minutes following IV administration and 4.5 +/- 1.5 minutes following IN administration. Mean bioavailability of BDZ following IN administration was 80 +/- 9%. Conclusions and Clinical Relevance-Diazepam is rapidly and efficiently abso rbed following IN administration of the parenteral formulation. Plasma conc entrations match or exceed the suggested therapeutic concentration (300 mu g/L). Intranasal administration of diazepam may be useful for treatment of seizures in dogs by owners or when intravenous access is not readily availa ble.