A useful approach for evaluating antitussive drugs in humans is to determine the sensitivity of the cough reflex to a standard challenge. The purpose of this study was to determine if methods used to induce coughing in humans would be effective when used on awake, untrained, healthy dogs for future application in therapeutic trials involving dogs with spontaneous disease. Methods tested were: mechanically stimulating the trachea by digital compression as well as by vibration from an electric shaver, neck massager, and palm sander (11 dogs), and administering nebulized irritant (3000 micromolar capsaicin), acidic (1 M citric acid), and hypotonic (deionized water) solutions using face masks (4 dogs). The threshold for success was defined as induction of at least 2 moderate or strong coughs in at least 75% of the dogs. None of the methods tested was successful. Digital compression induced soft (n = 2) or moderate (n = 1) coughing in 3 of 11 dogs tested. Nebulization of citric acid induced 1 soft cough in 1 of 4 dogs. It was concluded that coughing cannot be successfully induced in awake, healthy dogs using methods that are successful in humans. Other strategies must be developed so that cough sensitivity can be objectively and non-invasively measured in dogs for clinical research purposes.

Objective—To determine ocular tissue drug concentrations after topical ocular administration of 0.3% ciprofloxacin and 0.5% moxifloxacin in ophthalmologically normal horses. Animals—24 ophthalmologically normal adult horses. Procedures—0.3% ciprofloxacin and 0.5% moxifloxacin solutions (0.1 mL) were applied to the ventral conjunctival fornix of 1 eye in each horse as follows: group 1 (n = 8) at 0, 2, 4, and 6 hours; group 2 (8) at 0, 2, 4, 6, and 10 hours; and group 3 (8) at 0, 2, 4, 6, 10, and 14 hours. Tears, cornea, and aqueous humor (AH) were collected at 8, 14, and 18 hours for groups 1, 2, and 3, respectively. Drug concentrations were determined via high-performance liquid chromatography. Results—Median (25th to 75th percentile) concentrations of ciprofloxacin for groups 1, 2, and 3 in tears (μg/mL) were 53.7 (25.5 to 88.8), 48.5 (19.7 to 74.7), and 24.4 (15.4 to 67.1), respectively; in corneal tissue (μg/g) were 0.95 (0.60 to 1.02), 0.37 (0.32 to 0.47), and 0.48 (0.34 to 0.95), respectively; and in AH were lower than the limit of quantification in all groups. Concentrations of moxifloxacin for groups 1, 2, and 3 in tears (μg/mL) were 188.7 (44.5 to 669.2), 107.4 (41.7 to 296.5), and 178.1 (70.1 to 400.6), respectively; in corneal tissue (μg/g) were 1.84 (1.44 to 2.11), 0.78 (0.55 to 0.98), and 0.77 (0.65 to 0.97), respectively; and in AH (μg/mL) were 0.06 (0.04 to 0.08), 0.03 (0.02 to 0.05), and 0.02 (0.01 to 0.04), respectively. Corneal moxifloxacin concentrations were significantly higher in group 1 than groups 2 and 3. Conclusions and Clinical Relevance—After topical ocular administration, fluoroquinolones can reach therapeutic concentrations in tears and corneal tissue of horses, even when there is an intact epithelium.

Objective: To determine whether therapeutic concentrations of levetiracetam can be achieved in cats and to establish reasonable IV and oral dosing intervals that would not be associated with adverse effects in cats. Animals: 10 healthy purpose-bred cats. Procedures: In a randomized crossover study, levetiracetam (20 mg/kg) was administered orally and IV to each cat. Blood samples were collected 0, 10, 20, and 40 minutes and 1, 1.5, 2, 3, 4, 6, 9, 12, and 24 hours after administration. Plasma levetiracetam concentrations were determined via high-performance liquid chromatography. Results: Mean ± SD peak concentration was 25.54 ± 7.97 μg/mL. The mean y-intercept for IV administration was 37.52 ± 6.79 μg/mL. Half-life (harmonic mean ± pseudo-SD) was 2.95 ± 0.95 hours and 2.86 ± 0.65 hours for oral and IV administration, respectively. Mean volume of distribution at steady state was 0.52 ± 0.09 L/kg, and mean clearance was 2.0 ± 0.60 mL/kg/min. Mean oral bioavailability was 102 ± 39%. Plasma drug concentrations were maintained in the therapeutic range reported for humans (5 to 45 μg/mL) for at least 9 hours after administration in 7 of 10 cats. Only mild, transient hypersalivation was evident in some cats after oral administration. Conclusions and Clinical Relevance: Levetiracetam (20 mg/kg) administered orally or IV to cats every 8 hours should achieve and maintain concentrations within the therapeutic range for humans. Levetiracetam administration has favorable pharmacokinetics for clinical use, was apparently tolerated well, and may be a reasonable alternative antiepileptic drug in cats.

Objective—To evaluate the elimination pharmacokinetics of a single IM injection of a long-acting ceftiofur preparation (ceftiofur crystalline-free acid [CCFA]) in healthy adult helmeted guineafowl (Numida meleagris). Animals—14 healthy adult guineafowl. Procedures—1 dose of CCFA (10 mg/kg) was administered IM to each of the guineafowl. Blood samples were collected intermittently via jugular venipuncture over a 144-hour period. Concentrations of ceftiofur and all desfuroylceftiofur metabolites were measured in plasma via high-performance liquid chromatography. Results—No adverse effects of drug administration or blood collection were observed in any bird. The minimal inhibitory concentration (MIC) for many bacterial pathogens of poultry and domestic ducks (1 μg/mL) was achieved by 1 hour after administration in most birds and by 2 hours in all birds. A maximum plasma concentration of 5.26 μg/mL was reached 19.3 hours after administration. Plasma concentrations remained higher than the MIC for at least 56 hours in all birds and for at least 72 hours in all but 2 birds. The harmonic mean ± pseudo-SD terminal half-life of ceftiofur was 29.0 ± 4.93 hours. The mean area under the curve was 306 ± 69.3 μg•h/mL, with a mean residence time of 52.0 ± 8.43 hours. Conclusions and Clinical Relevance—A dosage of 10 mg of CCFA/kg, IM, every 72 hours in helmeted guineafowl should provide a sufficient plasma drug concentration to inhibit growth of bacteria with an MIC ≤ 1 μg/mL. Clinical use should ideally be based on bacterial culture and antimicrobial susceptibility data and awareness that use of CCFA in avian patients constitutes extralabel use of this product.