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

Platt, S.R.; Randell, S.C.; Scott, K.C.; Chrisman, C.L.; Hill, R.C.; Gronwall, R.R.

American Journal of Veterinary Research 61(6): 651-654

2000


ISSN/ISBN: 0002-9645
PMID: 10850840
DOI: 10.2460/ajvr.2000.61.651
Accession: 003389133

Six (4 male, 2 female) healthy adult Greyhounds were randomly assigned to 2 groups of 3 dogs in a crossover design. Diazepam (0.5 mg/kg of body weight) was administered i.v. 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 before and 3, 6, 9, 12, 15, 20, 30, 60, 120, 240 and 480 min following diazepam administration. After a 4-day washout period, dogs in group 1 received diazepam intranasally, dogs in group 2 received diazepam i.v. and blood was again collected. Plasma concentration of benzodiazepines (BDZ) was determined by use of a fluorescence polarization immunoassay. Mean peak plasma concentration of BDZ following i.v. administration (1316+or-216 micro g/litre) was greater than that following intranasal administration (448+or-41 micro g/litre). Time to peak concentration was <=3 min following i.v. administration and 4.5+or-1.5 min following intranasal administration. Mean bioavailability of BDZ following intranasal administration was 80+or-9%. It is concluded that diazepam is rapidly and efficiently absorbed following intranasal administration of the parenteral formulation. Plasma concentrations match or exceed the suggested therapeutic concentration (300 micro g/litre). Intranasal administration of diazepam may be useful for treatment of seizures in dogs by owners or when i.v. access is not readily available.

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