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  • Author or Editor: Ronald R. Gronwall x
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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)

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in American Journal of Veterinary Research

Abstract

Objective—To determine the disposition of orally administered cefpodoxime proxetil in foals and adult horses and measure the minimum inhibitory concentrations (MICs) of the drug against common bacterial pathogens of horses.

Animals—6 healthy adult horses and 6 healthy foals at 7 to 14 days of age and again at 3 to 4 months of age.

Procedure—A single dose of cefpodoxime proxetil oral suspension was administered (10 mg/kg) to each horse by use of a nasogastric tube. In 7- to 14-day-old foals, 5 additional doses were administered intragastrically at 12-hour intervals. The MIC of cefpodoxime for each of 173 bacterial isolates was determined by use of a commercially available test.

Results—In 7- to 14-day-old foals, mean ± SD time to peak serum concentration (Tmax) was 1.7 ± 0.7 hours, maximum serum concentration (Cmax) was 0.81 ± 0.22 µg/mL, and elimination half-life (harmonic mean) was 7.2 hours. Disposition of cefpodoxime in 3- to 4-month-old foals was not significantly different from that of neonates. Adult horses had significantly higher Cmax and significantly lower Tmax, compared with values for foals. The MIC of cefpodoxime required to inhibit growth of 90% of isolates for Salmonella enterica, Escherichia coli, Pasteurella spp, Klebsiella spp, and β-hemolytic streptococci was 0.38, 1.00, 0.16, 0.19, and 0.09 µg/mL, respectively.

Conclusions and Clinical Relevance—Oral administration at a dosage of 10 mg/kg every 6 to 12 hours would appear appropriate for the treatment of equine neonates with bacterial infections. (Am J Vet Res 2005;66:30–35)

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in American Journal of Veterinary Research

Abstract

Objective—To determine the pharmacokinetics of azithromycin and its concentration in body fluids and bronchoalveolar lavage cells in foals.

Animals—6 healthy 6- to 10-week-old foals.

Procedure—Azithromycin (10 mg/kg of body weight) was administered to each foal via IV and intragastric (IG) routes in a crossover design. After the first IG dose, 4 additional IG doses were administered at 24-hour intervals. A microbiologic assay was used to measure azithromycin concentrations in serum, peritoneal fluid, synovial fluid, pulmonary epithelial lining fluid (PELF), and bronchoalveolar (BAL) cells.

Results—Azithromycin elimination half-life was 20.3 hours, body clearance was 10.4 ml/min·kg, and apparent volume of distribution at steady state was 18.6 L/kg. After IG administration, time to peak serum concentration was 1.8 hours and bioavailability was 56%. After repeated IG administration, peak serum concentration was 0.63 ± 0.10 µg/ml. Peritoneal and synovial fluid concentrations were similar to serum concentrations. Bronchoalveolar cell and PELF concentrations were 15- to 170-fold and 1- to 16-fold higher than concurrent serum concentrations, respectively. No adverse reactions were detected after repeated IG administration.

Conclusions and Clinical Relevance—On the basis of pharmacokinetic values, minimum inhibitory concentrations of Rhodococcus equi isolates, and drug concentrations in PELF and bronchoalveolar cells, a single daily oral dose of 10 mg/kg may be appropriate for treatment of R equi infections in foals. Persistence of high azithromycin concentrations in PELF and bronchoalveolar cells 48 hours after discontinuation of administration suggests that after 5 daily doses, oral administration at 48-hour intervals may be adequate. (Am J Vet Res 2001;62:1870–1875)

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in American Journal of Veterinary Research