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

Simon R. Platt Department of Small Animal Clinical Sciences, College of Veterinary Medicine, University of Florida, Gainesville, FL 32610.
present address is the Department of Small Animal Medicine, College of Veterinary Medicine, University of Georgia, Athens, GA 30602-7390.

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Susan C. Randell Department of Small Animal Clinical Sciences, College of Veterinary Medicine, University of Florida, Gainesville, FL 32610.

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Karen C. Scott Department of Small Animal Clinical Sciences, College of Veterinary Medicine, University of Florida, Gainesville, FL 32610.

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Cheryl L. Chrisman Department of Small Animal Clinical Sciences, College of Veterinary Medicine, University of Florida, Gainesville, FL 32610.

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Richard C. Hill Department of Small Animal Clinical Sciences, College of Veterinary Medicine, University of Florida, Gainesville, FL 32610.

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Ronald R. Gronwall Department of Small Animal Clinical Sciences, College of Veterinary Medicine, University of Florida, Gainesville, FL 32610.

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Abstract

Objective—To determine whether plasma concentrations of benzodiazepines (BDZ) in dogs following intranasal (IN) administration of diazepam are comparable 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 before and 3, 6, 9, 12, 15, 20, 30, 60, 120, 240, and 480 minutes following diazepam administration. After a 4-day washout period, dogs in group 1 received 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 administration (1316 ± 216 µg/L) was greater than that following IN administration (448 ± 41 µg/L). Time to peak concentration was ≤ 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 absorbed following IN administration of the parenteral formulation. Plasma concentrations match or exceed the suggested therapeutic concentration (300 µg/L). Intranasal administration of diazepam may be useful for treatment of seizures in dogs by owners or when intravenous access is not readily available. (Am J Vet Res 2000;61:651–654)

Abstract

Objective—To determine whether plasma concentrations of benzodiazepines (BDZ) in dogs following intranasal (IN) administration of diazepam are comparable 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 before and 3, 6, 9, 12, 15, 20, 30, 60, 120, 240, and 480 minutes following diazepam administration. After a 4-day washout period, dogs in group 1 received 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 administration (1316 ± 216 µg/L) was greater than that following IN administration (448 ± 41 µg/L). Time to peak concentration was ≤ 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 absorbed following IN administration of the parenteral formulation. Plasma concentrations match or exceed the suggested therapeutic concentration (300 µg/L). Intranasal administration of diazepam may be useful for treatment of seizures in dogs by owners or when intravenous access is not readily available. (Am J Vet Res 2000;61:651–654)

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