Objective—To evaluate markers of in vivo platelet function (urinary 11-dehydro-thromboxane B2 [11-dehydroTXB2] and 2,3-dinorTXB2) and assess their response to administration of 2 commonly used dosages of aspirin in healthy dogs. Animals—20 healthy dogs. Procedures—Urine was collected prior to aspirin administration and on the morning following the last evening administration. Twenty dogs received aspirin (1 mg/kg, PO, q 24 h) for 7 consecutive doses. After a washout period of 5 months, 10 dogs received a single dose of aspirin (10 mg/kg, PO). Concentrations of urinary thromboxane metabolites 11-dehydroTXB2 and 2,3-dinorTXB2 were measured via ELISA, and values were normalized to urine creatinine concentration. Results—Median baseline 11-dehydroTXB2 concentrations were 0.38 ng/mg of creatinine (range, 0.15 to 1.13 ng/mg). Mean ± SD baseline 2 at a 3-dinorTXB2 concentrations were 6.75 ± 2.77 ng/mg of creatinine. Administration of aspirin at a dosage of 1 mg/kg, PO, every 24 hours for 7 days did not significantly decrease urinary 11-dehydroTXB2 concentration, but administration of the single aspirin dose of 10 mg/kg did significantly decrease 11-dehydroTXB2 concentration by a median of 45.5% (range, 28.2% to 671%). Administration of the 1 mg/kg aspirin dosage significantly decreased urinary 2,3-dinorTXB2 concentration by a mean ± SD of 33.0 ± 23.7%. Administration of the single aspirin dose of 10 mg/kg also significantly decreased 2,3-dinorTXB2 concentration by a mean ± SD of 46.7 ± 12.6%. Conclusions and Clinical Relevance—Aspirin administration (1 mg/kg/d) may be insufficient for reliable platelet inhibition in healthy dogs.

This was a preliminary investigation of the use of lithium to prevent lomustine-induced myelosuppression. Four 10 to 11 kg beagles received lomustine 20 to 30 mg, PO, q3wk, with cephalexin prophylaxis. Two dogs also received lithium, 150 to 300 mg, PO, q12h. Lithium blood concentrations fluctuated in and out of therapeutic interval. Lithium was discontinued in one dog in week 13, and in the other dog in week 38, due to toxicoses. All dogs developed grade 1 to 4 neutropenia after each lomustine treatment. In dogs receiving lomustine only, platelet concentrations decreased from 274 and 293 × 10(9)/L in week 1, to 178 and 218 × 10(9)/L in weeks 38 and 13, respectively. In dogs receiving lomustine and lithium, platelet concentrations decreased from 351 and 288 × 10(9)/L in week 1, to 214 and 212 × 10(9)/L, in weeks 36 and 13, respectively. Lithium did not prevent lomustine-induced myelosuppression and had important side-effects.

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 compare results of body condition scoring by use of a 9-point scale with body composition determined by dual-energy x-ray absorptiometry (DEXA) in indoor-confined neutered domestic shorthair (DSH) pet cats. Animals—72 indoor-confined, adult neutered DSH pet cats (38 females and 34 males). Procedures—All cats underwent a physical examination including assessment of body weight (BW), body condition score (BCS; 1 = emaciated, 5 = ideal, and 9 = grossly obese), and girth. Urinalysis, CBC, and serum biochemical analysis were also performed. After the cats were confirmed healthy, they were anesthetized for body composition measurement via DEXA. Lean body mass, fat mass, and percentage body fat (%BF) were then evaluated. Results—The correlation between %BF and BCS (r = 0.87) was superior to the correlations between %BFand BW (r = 0.74) and between %BF and girth (r = 0.78). Values for %BF differed significantly between all pairs of BCSs except BCSs 8 and 9. Within a BCS, the %BF was similar for male and female cats. The mean %BF for cats with a BCS of 5 was 32, which exceeded the upper reference limit of %BF generally considered ideal (30). Conclusions and Clinical Relevance—The 9-point BCS scale appears useful for assessing %BF in DSH pet cats. Nevertheless, study findings could indicate a need for redefining the ideal BCS for inactive neutered cats to include a BCS of 4.

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 the analgesic and systemic effects of thoracic epidural administration of ketamine, lidocaine, or both in conscious dogs. Animals—6 adult mixed-breed dogs. Procedures—Each dog received 2% lidocaine hydrochloride without epinephrine (3.8 mg/kg), 5% ketamine hydrochloride (3.0 mg/kg), or both in randomized order with = 1 week between treatments. Drugs were administered in a total volume of 0.25 mL/kg through a thoracic epidural catheter implanted via the lumbosacral approach. Heart rate, blood pressure, respiratory rate, rectal temperature, analgesia, sedation, and ataxia were determined before treatment (baseline [time 0]) and at 5, 10, 15, 20, 30, 40, 50, 60, 90, 120, 150, and 180 minutes after administration. Results—The main areas of analgesia for the 3 treatments were the thorax and forelimbs bilaterally. Median duration of analgesia was shorter after administration of ketamine (30 minutes) than after administration of lidocaine (40 minutes) and lidocaine plus ketamine (90 minutes). All treatments caused moderate motor blockade, and only the ketamine and lidocaine plus ketamine treatments caused mild sedation. Significant decreases in systolic and mean arterial blood pressure were observed only with the lidocaine plus ketamine treatment. Conclusions and Clinical Relevance—Thoracic epidural administration of lidocaine plus ketamine resulted in longer duration of analgesia of the thorax and forelimbs bilaterally in conscious dogs, compared with administration of ketamine or lidocaine alone. Additional studies are needed to determine whether this technique adequately relieves postoperative pain after thoracic surgical procedures and whether it causes respiratory depression in dogs.

Objective—To determine whether oral administration of metoclopramide or a commercially available powdered whole grapefruit (PWG) nutraceutical in combination with cyclosporine enhances systemic availability of cyclosporine in dogs. Sample—8 healthy mixed-breed dogs in part 1 and 6 of these 8 dogs in part 2. Procedures—Cyclosporine pharmacokinetics were determined over the course of 24 hours after oral administration of cyclosporine (5 mg/kg) alone, cyclosporine with metoclopramide (0.3 to 0.5 mg/kg), cyclosporine with 2 g of PWG, or cyclosporine combined with both metoclopramide and 2 g of PWG by use of a Latin square crossover study with a 14-day washout period between treatments. Sixty days later, 6 of the 8 dogs were given 10 g of PWG followed by cyclosporine, and pharmacokinetic parameters were compared with those previously obtained after administration of cyclosporine alone. Results—Although metoclopramide or coadministration of metoclopramide and 2 g of PWG had no effect on the pharmacokinetic parameters of cyclosporine, compared with results for cyclosporine alone, the higher (10-g) dose of PWG resulted in 29% faster mean time to maximal plasma cyclosporine concentration, 54% larger area under the curve, and 38% lower apparent oral clearance. Conclusions and Clinical Relevance—Adjustment of the cyclosporine dose may not be needed when metoclopramide is coadministered orally to prevent common adverse effects of cyclosporine. Powdered whole grapefruit has the potential to reduce the required orally administered dose of cyclosporine but only when PWG is used in an amount (at least 10 g) that is currently not cost-effective.

Objective--To determine whether joint lavage performed simultaneously with IV regional limb perfusion (IVRLP) reduces the effectiveness of IVRLP and to compare 2 types of tourniquets used for this procedure in horses. Animal--11 adult horses. Procedures--2 groups of 6 horses were tested by use of a pneumatic or an Esmarch tourniquet (1 horse was tested twice [once in each group]). Standing IVRLP with amikacin (500 mg) was performed for 30 minutes. Simultaneously, the metacarpophalangeal joint was lavaged with 2 L of lactated Ringer's solution and the egress fluids were collected. Samples of the distal interphalangeal joint synovial fluid and blood from the digital and jugular veins were collected at set time intervals. Amikacin concentrations in all fluids were determined via fluorescence polarization immunoassay. Results--Less amikacin was measured in the systemic circulation with the Esmarch tourniquet than with the pneumatic tourniquet. Amikacin concentrations in the synovial fluid from the distal interphalangeal joints of the Esmarch tourniquet group ranged from 45.1 to 1,968 μg/mL and in the pneumatic tourniquet group ranged from 1.7 to 92.3 μg/mL after 30 minutes of IVRLP. Total loss of amikacin in the egress fluids from the joint lavage ranged from < 1.36 to 7.72 mg for the Esmarch tourniquet group and from < 1.20 to 1.75 mg for the pneumatic tourniquet group. Conclusions and Clinical Relevance--On standing horses, IVRLP performed simultaneously with joint lavage resulted in negligible loss of amikacin in the egress lavage fluids. The Esmarch tourniquet was more effective in preventing loss of amikacin from the distal portion of the limb, easier to use, and less expensive than the pneumatic tourniquet.

Objective—To determine whether trilostane or ketotrilostane is more potent in dogs and determine the trilostane and ketotrilostane concentrations that inhibit adrenal gland cortisol, corticosterone, and aldosterone secretion by 50%. Sample—24 adrenal glands from 18 mixed-breed dogs. Procedures—Adrenal gland tissues were sliced, placed in tissue culture, and stimulated with 100 pg of ACTH/mL alone or with 5 concentrations of trilostane or ketotrilostane. Trials were performed independently 4 times. In each trial, 6 samples (1 for each time point) were collected for each of the 5 concentrations of trilostane and ketotrilostane tested as well as a single negative control samples. At the end of 0, 1, 2, 3, 5, and 7 hours, tubes were harvested and media and tissue slices were assayed for cortisol, corticosterone, aldosterone, and potassium concentrations. Data were analyzed via pharmacodynamic modeling. One adrenal slice exposed to each concentration of trilostane or ketotrilostane was submitted for histologic examination to assess tissue viability. Results—Ketotrilostane was 4.9 and 2.4 times as potent in inhibiting cortisol and corticosterone secretion, respectively, as its parent compound trilostane. For trilostane and ketotrilostane, the concentrations that inhibited secretion of cortisol or corticosterone secretion by 50% were 480 and 98.4 ng/mL, respectively, and 95.0 and 39.6 ng/mL, respectively. Conclusions and Clinical Relevance—Ketotrilostane was more potent than trilostane with respect to inhibition of cortisol and corticosterone secretion. The data should be useful in developing future studies to evaluate in vivo serum concentrations of trilostane and ketotrilostane for efficacy in the treatment of hyperadrenocorticism.

The aim of this study was to evaluate the performance characteristics of an automated immunoassay for canine insulin-like growth factor 1 (IGF-1) measurement and to investigate the possible effects of some sources of variation, such as diurnal variations, feeding/fasting cycles, and glucocorticoid administration, in dogs. The immunoassay evaluated had an adequate analytical performance with intra- and inter-assay coefficients of variation (CVs) lower than 10%, linear regression equations with correlation coefficients of 0.9993 and 0.9988 after serial dilutions, and a limit of quantification of 7.1 ng/mL that was even lower than that reported by the manufacturer. The assay was significantly affected by hemolysis and lipemia producing a significant decrease in IGF-1 concentrations, but not by bilirubinemia. Serum IGF-1 concentrations did not show significant diurnal changes in fed or fasted dogs and were not affected by glucocorticoid administration.