Objective-To determine the pharmacokinetics and safety of meloxicam in rabbits when administered orally for 29 days. Animals-6 healthy rabbits. Procedures-Meloxicam (1.0 mg/kg, PO, q 24 h) was administered to rabbits for 29 days. Blood was collected immediately before (time 0) and 2, 4, 6, 8, and 24 hours after drug administration on days 1, 8, 15, 22, and 29 to evaluate the pharmacokinetics of meloxicam. On day 30, an additional sample was collected 36 hours after treatment. Plasma meloxicam concentrations were quantified with liquid chromatography–mass spectrometry, and noncompartmental pharmacokinetic analysis was performed. Weekly plasma biochemical analyses were performed to evaluate any adverse physiologic effects. Rabbits were euthanatized for necropsy on day 31. Results-Mean +/- SD peak plasma concentrations of meloxicam after administration of doses 1, 8, 15, 22, and 29 were 0.67 +/- 0.19 μg/mL, 0.81 +/- 0.21 μg/mL, 1.00 +/- 0.31 μg/mL, 1.00 +/- 0.29 μg/mL, and 1.07 +/- 0.19 μg/mL, respectively; these concentrations did not differ significantly among doses 8 through 29. Results of plasma biochemical analyses were within reference ranges at all time points evaluated. Gross necropsy and histologic examination of tissues revealed no clinically relevant findings. Conclusions and Clinical Relevance-Plasma concentrations of meloxicam for rabbits in the present study were similar to those previously reported in rabbits that received 1. 0 mg of meloxicam/kg, PO every 24 hours, for 5 days. Results suggested that a dosage of 1. 0 mg/kg, PO, every 24 hours for up to 29 days may be safe for use in healthy rabbits.

Objective-To evaluate the thermal antinociceptive and sedative effects and duration of action of tramadol hydrochloride after oral administration to American kestrels (Falco sparverius). Animals-12 healthy 3-year-old American kestrels. Procedures-Tramadol (5, 15, and 30 mg/kg) and a control suspension were administered orally in a masked randomized crossover experimental design. Foot withdrawal response to a thermal stimulus was determined 1 hour before (baseline) and 0.5, 1.5, 3, 6, and 9 hours after treatment. Agitation-sedation scores were determined 3 to 5 minutes before each thermal stimulus test. Results-The lowest dose of tramadol evaluated (5 mg/kg) significantly increased the thermal foot withdrawal thresholds for up to 1.5 hours after administration, compared with control treatment values, and for up to 9 hours after administration, compared with baseline values. Tramadol at doses of 15 and 30 mg/kg significantly increased thermal thresholds at 0.5 hours after administration, compared with control treatment values, and up to 3 hours after administration, compared with baseline values. No significant differences in agitation-sedation scores were detected between tramadol and control treatments. Conclusions and Clinical Relevance-Results indicated oral administration of 5 mg of tramadol/kg significantly increased thermal nociception thresholds for kestrels for 1.5 hours, compared with a control treatment, and 9 hours, compared with baseline values; higher doses resulted in less pronounced antinociceptive effects. Additional studies with other types of stimulation, formulations, dosages, routes of administration, and testing times would be needed to fully evaluate the analgesic and adverse effects of tramadol in kestrels and other avian species.

The effects of heparin administration, by the oral route, were evaluated in dogs. In single and multiple dose studies (single 7.5 mg/kg, multiple 3 × 7.5 mg/kg per 48 h), plasma, urine, and fecal samples were collected at various times up to 120 h after oral administration of unfractionated heparin. Changes in plasma and urine anti-Xa activity, plasma and urine anti-IIa activity, plasma activated partial thromboplastin time (APTT) and antithrombin (ATIII), and chemical heparin in urine and feces were examined with time. There was support for heparin absorption, with significant differences in APTT, heparin in plasma as determined by anti-Xa activity (Heptest) in the single dose study and plasma anti-Xa activity, anti-IIa activity and ATIII; and chemical heparin in urine in the multiple dose study. No clinical evidence of bleeding was detected in any dog during the studies. Oral heparin therapy may be applicable for thromboembolic disease in animals. Further studies are warranted to determine the effects of oral heparin at the endothelial level in the dog.

The objective of the present work was to determine the effect of Lactobacillus murinus strain LbP2 on canine fecal immunoglobulin A (IgA) levels. Seven dogs were orally treated with a 3-mL suspension of L. murinus LbP2 containing 5 x 109 colony-forming units on alternate days for 2 wk. Six dogs were treated with 3 mL of phosphate-buffered saline as placebo. Fecal samples were taken from the rectal ampulla on days 0 and 16, and the total canine fecal IgA concentration was determined with an immunoperoxidase assay kit. The IgA levels of individual dogs were compared with the nonparametric Wilcoxon test. Differences were considered significant when the P-value was less than 0.05. An increase in the total fecal IgA concentration was observed in the 7 dogs after treatment with L. murinus LbP2 (P = 0.01796). No differences were detected between the initial total fecal IgA values and those obtained at the end of placebo treatment. Thus, after oral administration L. murinus LbP2 showed potential immunomodulatory effects, an important property to assess in a microorganism being considered for use as a probiotic.

Objective—To evaluate the effects of cisapride and metoclopramide hydrochloride administered orally on the lower esophageal sphincter (LES) resting pressure in awake healthy dogs. Animals—6 adult Beagles. Procedures—Each dog was evaluated after administration of a single dose of cisapride (0.5 mg/kg), metoclopramide (0.5 mg/kg), or placebo (empty gelatin-free capsule) in 3 experiments performed at 3-week intervals. To measure LES pressure, a high-resolution manometry catheter equipped with 40 pressure sensors spaced 10 mm apart was used. For each experiment, LES pressure was recorded during a 20-minute period with a virtual electronic sleeve emulation before treatment (baseline) and at 1, 4, and 7 hours after drug or placebo administration. A linear mixed-effects model was used to test whether the 3 treatments affected LES pressure differently. Results—In the cisapride, metoclopramide, and placebo experiments, median baseline LES pressures were 29.1, 30.5, and 29.0 mm Hg, respectively. For the cisapride, metoclopramide, and placebo treatments, median LES pressures at 1 hour after administration were 44.4, 37.8, and 36.6 mm Hg, respectively; median LES pressures at 4 hours after administration were 50.7, 30.6, and 31.1 mm Hg, respectively; and median LES pressures at 7 hours after administration were 44.3, 28.5, and 33.3 mm Hg, respectively. The LES pressures differed significantly only between the placebo and cisapride treatments. Conclusions and Clinical Relevance—Results suggested that orally administered cisapride may be of benefit in canine patients for which an increase in LES pressure is desirable, whereas orally administered metoclopramide did not affect LES resting pressures in dogs.

Objective-To determine pharmacodynamic cutoffs with pharmacokinetic-pharmacodynamic principles and Monte Carlo simulation (MCS) for use of amoxicillin in pigs to set interpretive criteria for antimicrobial susceptibility testing. Sample-191 plasma disposition curves of amoxicillin obtained from 21 IV, 104 IM, and 66 PO administrations corresponding to 2,098 plasma concentrations. Procedures-A population model of amoxicillin disposition in pigs was developed for PO and IM administration. The MCS method was then used to determine, for various dosage regimens, the proportion of pigs achieving plasma amoxicillin concentrations greater than a selection of possible minimal inhibitory concentrations (MICs) ranging from 0.0625 to 4 mg/L for at least 40% of a 24-hour period. Results-A target attainment rate (TAR) of 90% was never achieved with the breakpoint recommended by the Clinical and Laboratory Standards Institute (0.5 mg/L) when the usual recommended dosage (20 mg/kg/d) was used. Only by dividing the orally administered daily dose into 12-hour administration intervals was a TAR > 90% achieved when the total dose was at least 40 mg/kg for a pathogen having an MIC ≤ 0.0625 mg/L. For the IM route, the TAR of 90% could only be achieved for MICs of 0.0625 and 0.125 mg/L with the use of 15 and 30 mg/kg doses, respectively. Conclusions and Clinical Relevance-Population kinetics and MCS are required to determine robust species-specific interpretive criteria (susceptible, intermediate, and resistant classifications) for antimicrobial susceptibility testing breakpoints (taking into account interanimal variability).