Objective-To determine the pharmacokinetics, pharmacodynamics, and safety of zoledronic acid in horses. Animals-8 healthy horses. Procedures-A single dose of zoledronic acid (0.057 mg/kg, IV) was administered during a 30-minute period. Venous blood was collected at several time points. Zoledronic acid concentration in plasma was measured by liquid chromatography-tandem mass spectrometry, and pertinent pharmacokinetic parameters were determined. Plasma was analyzed for total calcium, BUN, and creatinine concentrations and a marker for bone resorption (C-terminal telopeptides of type I collagen). Results-Zoledronic acid was safely administered IV during a 30-minute period, and no adverse effects were observed. Plasma concentrations of zoledronic acid were consistent with a 2-compartment mammillary model. Plasma concentrations of zoledronic acid were detected for up to 8 hours after administration. Mean total calcium concentrations in plasma were less than the reference range 7 days after zoledronic acid administration. A marker for bone remodeling decreased in concentration after zoledronic acid administration and remained low for the 1-year duration of the study. No changes in BUN and creatinine concentrations were observed after zoledronic acid administration. Conclusions and Clinical Relevance-Zoledronic acid was safely administered in healthy horses. Zoledronic acid is reported as the strongest bisphosphonate presently available, and studies evaluating potential benefits of zoledronic acid in horses with orthopedic conditions are warranted.

Oxidative stress is a key component in the immunosuppression of chronic kidney disease (CKD), and neutrophil function may be impaired by oxidative stress. To test the hypothesis that in uremic dogs with CKD, oxidative stress is increased and neutrophils become less viable and functional, 18 adult dogs with CKD were compared with 15 healthy adult dogs. Blood count and urinalysis were done, and the serum biochemical profile and plasma lipid peroxidation (measurement of thiobarbituric acid reactive substances) were determined with the use of commercial reagents. Plasma total antioxidant capacity (TAC) was measured with a spectrophotometer and commercial reagents, superoxide production with a hydroethidine probe, and the viability and apoptosis of neutrophils with capillary flow cytometry and the annexin V-PE system. The plasma concentrations of cholesterol (P = 0.0415), creatinine (P < 0.0001), and urea (P < 0.0001) were significantly greater in the uremic dogs than in the control dogs. The hematocrit (P = 0.0004), urine specific gravity (P = 0.015), and plasma lipid peroxidation (P < 0.0001) were significantly lower in the dogs that were in late stages of CKD than in the control group. Compared with those isolated from the control group, neutrophils isolated from the CKD group showed a higher rate of spontaneous (0.10 ± 0.05 versus 0.49 ± 0.09; P = 0.0033; median ± standard error of mean) and camptothecin-induced (18.53 ± 4.06 versus 44.67 ± 4.85; P = 0.0066) apoptosis and lower levels of superoxide production in the presence (1278.8 ± 372.8 versus 75.65 ± 86.6; P = 0.0022) and absence (135.29 ± 51.74 versus 41.29 ± 8.38; P = 0.0138) of phorbol-12-myristate-13-acetate stimulation. Thus, oxidative stress and acceleration of apoptosis occurs in dogs with CKD, the apoptosis diminishing the number of viable neutrophils and neutrophil superoxide production.

Objective-To determine whether tepoxalin alters kidney function in dogs with chronic kidney disease (CKD). Animals-16 dogs with CKD (International Renal Interest Society stage 2 or 3) and osteoarthritis. Procedures-Kidney function was assessed via serum biochemical analysis, urinalysis, urine protein-to-creatinine concentration ratio, urine γ-glutamyl transpeptidase-to-creatinine concentration ratio, iohexol plasma clearance, and indirect blood pressure measurement twice before treatment. Dogs received tepoxalin (10 mg/kg, PO, q 24 h) for 28 days (acute phase; n = 16) and an additional 6 months (chronic phase; 10). Recheck examinations were performed weekly (acute phase) and at 1, 3, and 6 months (chronic phase). Kidney function variables were analyzed via repeated-measures ANOVA. Results-There was no difference over time for any variables in dogs completing both phases of the study. Adverse drug events (ADEs) resulting in discontinuation of tepoxalin administration included increased serum creatinine concentration (1 dog; week 1), collapse (1 dog; week 1), increased liver enzyme activities (1 dog; week 4), vomiting and diarrhea (1 dog; week 8), hematochezia (1 dog; week 24), and gastrointestinal ulceration or perforation (1 dog; week 26). Preexisting medical conditions and concomitant drug use may have contributed to ADEs. Kidney function was not affected in the latter 5 dogs. Discontinuation of tepoxalin administration stabilized kidney function in the former dog and resolved the ADEs in 4 of the 5 latter dogs. Conclusions and Clinical Relevance-Tepoxalin may be used, with appropriate monitoring, in dogs with International Renal Interest Society stage 2 or 3 CKD and osteoarthritis.