Comparison of plasma benzodiazepine concentrations following intranasal and intravenous administration of diazepam to dogs.
OBJECTIVE
To determine whether plasma concentrations of benzodiazepines (BDZ) in dogs following intranasal (IN) administration of diazepam are comparable to concentrations following IV administration.


METHODS
6 (4 male, 2 female) healthy adult Greyhounds.


METHODS
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 (1,316 +/- 216 microg/L) was greater than that following IN administration (448 +/- 41 microg/L). Time to peak concentration was < or = 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
Diazepam is rapidly and efficiently absorbed following IN administration of the parenteral formulation. Plasma concentrations match or exceed the suggested therapeutic concentration (300 microg/L). Intranasal administration of diazepam may be useful for treatment of seizures in dogs by owners or when intravenous access is not readily available.
Platt
S R
SR
Department of Small Animal Clinical Sciences, College of Veterinary Medicine, University of Florida, Gainesville 32610, USA.
Randell
S C
SC
Scott
K C
KC
Chrisman
C L
CL
Hill
R C
RC
Gronwall
R R
RR
D000281:Administration, Intranasal; D000818:Animals; D000927:Anticonvulsants / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use; D019540:Area Under Curve; D018592:Cross-Over Studies; D003975:Diazepam / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use; D004285:Dogs / Q000378:metabolism*; D005260:Female; D016231:Fluorescence Polarization Immunoassay / Q000662:veterinary; D006207:Half-Life; D007275:Injections, Intravenous / Q000662:veterinary; D008297:Male; D011897:Random Allocation; D013226:Status Epilepticus / Q000188:drug therapy / Q000662:veterinary
D000927:Anticonvulsants; D003975:Diazepam