Lisa R. Reynolds

Effects of meloxicam on plasma iohexol clearance as a marker of glomerular filtration rate in conscious healthy cats

OBJECTIVE To investigate the effect of therapeutic dosages of meloxicam on the plasma clearance of iohexol in healthy, euvolemic, conscious cats fed a sodium-replete diet. ANIMALS 6 healthy adult neutered male cats. PROCEDURES For each treatment period in a masked, randomized, crossover study, cats were administered either no treatment or meloxicam. Iohexol clearance studies were performed before the treatment period began (baseline) and on the final day of the treatment period. Iohexol concentrations were determined by use of a high-performance liquid chromatography assay, and plasma iohexol clearance as a marker of glomerular filtration rate was calculated by use of a 1-compartment model. RESULTS No significant treatment effect was detected. Mean +/- SE iohexol clearance for cats administered meloxicam (3.31 +/- 0.27 mL/min/kg) was not significantly different from mean baseline value for the meloxicam treatment period (3.07 +/- 0.32 mL/min/kg). CONCLUSIONS AND CLINICAL RELEVANCE In this study, short-term meloxicam administration did not measurably alter the glomerular filtration rate as assessed via plasma clearance of iohexol. This suggests that renal prostaglandins in cats did not have a measurable effect on glomerular filtration rates in healthy, euvolemic, conscious states as determined on the basis of methods used in this study.

Lack of inhibitory effect of acetylsalicylic acid and meloxicam on whole blood platelet aggregation in cats.

OBJECTIVE To determine the effects of acetylsalicylic acid (ASA) and meloxicam on feline platelet aggregation and associated platelet thromboxane production and serotonin release. DESIGN Prospective interventional study. SETTING University research facility. ANIMALS Eight healthy male castrated domestic short hair cats from a research colony. INTERVENTIONS Oral medications were administered to 8 cats for 14 days in a randomized, placebo-controlled, crossover design. Treatment groups included: aspirin (ASA) (5 mg/kg q 48 h), meloxicam (0.05 mg/kg q 24 h), and placebo (0.5 mL of water q 24 h). Thromboxane assays (TXB(2) ) and whole blood (impedance) aggregometry (WBA) were performed on samples collected before drug administration, and on days 7, 15, and 17, using adenosine diphosphate (ADP; 10 μM) and collagen (5 μg/mL) as agonists for WBA. Serotonin release was assayed on postaggregation plasma. Oral mucosal bleeding time (OMBT) and complete blood cell counts were measured on days 0 and 15. MEASUREMENTS AND MAIN RESULTS Neither medication affected WBA at any time point. OMBT decreased in the ASA group relative to baseline. No differences were detected in WBA and OMBT baseline between any groups. No difference was detected in serotonin secretion at any time point. TXB(2) was significantly decreased in the ASA group at all times after initiation of treatment but no change was noted in the meloxicam or placebo groups. CONCLUSIONS At the doses studied, neither meloxicam nor ASA had an inhibitory effect on WBA or OMBT in cats. Thromboxane concentrations were significantly decreased with ASA treatment.

Effects of firocoxib, meloxicam, and tepoxalin on prostanoid and leukotriene production by duodenal mucosa and other tissues of osteoarthritic dogs.

OBJECTIVE To evaluate the in vivo effects of firocoxib, meloxicam, and tepoxalin on prostaglandin (PG) and leukotriene production in duodenal mucosa and other target tissues in dogs with chronic osteoarthritis (OA). ANIMALS 8 dogs with chronic, unilateral OA of the stifle joint. PROCEDURES In a crossover design, each dog received placebo (no treatment), firocoxib, meloxicam, or tepoxalin for 7 days, followed by a 21-day washout period. On the first day of treatment (day 0; baseline) and days 2, 4, and 7, samples of whole blood, synovial fluid, and gastric and duodenal mucosae were collected. Prostaglandin E2 concentrations were measured in synovial fluid of the stifle joint and after ex vivo stimulation of whole blood samples. Synthesis of PGE1 and PGE2 was measured in samples of gastric and duodenal mucosae. Concentrations of thromboxane B2 (TxB2) were measured in whole blood samples. Leukotriene B4 (LTB4) concentrations were measured in samples of whole blood (ex vivo stimulation) and gastric and duodenal mucosae. RESULTS Firocoxib, meloxicam, and tepoxalin significantly suppressed whole blood concentrations of PGE2, compared with baseline and placebo concentrations, at days 2, 4, and 7. Tepoxalin significantly suppressed serum TxB2 concentrations, compared with baseline, firocoxib, meloxicam, and placebo, at all 3 time points. Production of PGE1 and PGE2 was significantly lower in duodenal versus gastric mucosa. Tepoxalin significantly decreased rates of PGE1 and PGE2 in duodenal and gastric mucosae, compared with baseline rates. CONCLUSIONS AND CLINICAL RELEVANCE PG production was lower in the duodenum than in the stomach. Firocoxib had a COX-1-sparing effect in vivo.

Comparison of overground and treadmill-based gaits of dogs

OBJECTIVE To compare overground and treadmill-based gaits of dogs. ANIMALS 5 clinically normal adult mixed-breed dogs. PROCEDURES To obtain dynamic gait data, 30 retroreflective markers were affixed bilaterally to specific regions of the hind limbs and pelvis of each dog. For each dog, 3-D joint motion data (sagittal [flexion and extension], transverse [internal and external rotation], and frontal [abduction and adduction] planes of motion) for the hip, femorotibial, and tarsal joints were acquired during walking and trotting through a calibrated testing space overground or on a treadmill. Comparison of data was performed via generalized indicator function analysis and Fourier analysis. RESULTS Both overground and treadmill-based gaits produced similar waveforms in all planes of motion. Fourier analysis revealed no difference between overground and treadmill-based gaits in the sagittal plane of motion; however, small differences were detected between overground and treadmill-based gaits in the other 2 planes of motion. Additionally, femorotibial joint motion during walking did not differ among planes of motion. Generalized indicator function analysis was able to detect differences between overground and treadmill-based gait waveforms in all planes of motion for all joints during walking and trotting. CONCLUSIONS AND CLINICAL RELEVANCE In dogs, overground and treadmill-based gaits produced similar waveform shapes. Of the 3 planes of motion evaluated, only sagittal plane kinematic gait data were unaffected by mode of ambulation as determined via Fourier analysis. Sagittal kinematic gait data collected from dogs during overground or treadmill-based ambulation were comparable. However, analysis methods may affect data comparisons.

Efficacy of ABT-116, an antagonist of transient receptor potential vanilloid type 1, in providing analgesia for dogs with chemically induced synovitis

OBJECTIVE To investigate the ability of ABT-116 (a proprietary antagonist of transient receptor potential vanilloid type 1) administered at 2 doses to attenuate lameness in dogs with experimentally induced urate synovitis. ANIMALS 8 purpose-bred mixed-breed dogs. PROCEDURES In a 4-way crossover study, dogs orally received each of low-dose ABT-116 treatment (LDA; 10 mg/kg), high-dose ABT-116 treatment (HDA; 30 mg/kg), firocoxib (5 mg/kg), and no treatment (nontreatment) once a day for 2 days, in a randomly assigned order. Synovitis was induced on the second day of each treatment period by intra-articular injection of either stifle joint with sodium urate, alternating between joints for each treatment period, beginning with the left stifle joint. Ground reaction forces, clinical lameness scores, and rectal temperature were assessed before the injection (baseline) and at various points afterward. RESULTS Lameness scores at the 2-, 6-, and 12-hour assessment points were higher than baseline scores for HDA and nontreatment, whereas scores at the 2- and 6-hour points were higher than baseline scores for LDA. For firocoxib, there was no difference from baseline scores in lameness scores at any point. Compared with baseline values, peak vertical force and vertical impulse were lower at 2 and 6 hours for HDA and nontreatment and at 2 hours for LDA. No changes in these values were evident for firocoxib. The HDA or LDA resulted in higher rectal temperatures than did treatment with firocoxib or nothing, but those temperatures did not differ among treatments. CONCLUSIONS AND CLINICAL RELEVANCE HDA had no apparent effect on sodium urate-induced lameness; LDA did attenuate the lameness but not as completely as firocoxib treatment. High rectal temperature is an adverse effect of oral ABT-116 administration that may be of clinical concern.

Effects of firocoxib, meloxicam, and tepoxalin administration on eicosanoid production in target tissues of healthy cats.

OBJECTIVE To evaluate the effects of firocoxib, meloxicam, and tepoxalin administration in healthy cats by measuring the ability of stimulated tissues to synthesize eicosanoids ex vivo. ANIMALS 8 healthy adult male cats. PROCEDURES In a blinded, randomized, crossover study design, cats were treated with firocoxib (1 mg/kg, PO, q 24 h), meloxicam (0.05 mg/kg, PO, q 24 h), tepoxalin (5.0 mg/kg, PO, q 12 h), or a placebo for 8 days. Blood samples and gastric and duodenal mucosal biopsy specimens were collected on days 0 (baseline; immediately before treatment), 3, and 8 of each treatment period. Thromboxane B2 (TXB2) concentrations were measured in serum, and prostaglandin E2 (PGE2) and leukotriene B4 (LTB4) concentrations were measured in plasma. Prostaglandin E1 (PGE1) synthesis, PGE2 synthesis, and LTB4 concentrations were measured in mucosal biopsy specimens. A 21-day minimum washout period was observed between treatments. Repeated-measures analyses were performed. RESULTS Firocoxib and meloxicam administration resulted in a lower plasma PGE2 concentration than at baseline on days 3 and 8 of administration, whereas tepoxalin administration did not. Tepoxalin administration resulted in a lower serum TXB2 concentration and pyloric and duodenal PGE1 synthesis on both days, compared with baseline and placebo administration. Neither firocoxib nor meloxicam administration altered pyloric or duodenal PGE1 synthesis on either day, compared with placebo administration. Tepoxalin administration also resulted in lower pyloric mucosal LTB4 concentrations on both days, compared with baseline values. CONCLUSIONS AND CLINICAL RELEVANCE Firocoxib and meloxicam administration had no effect on cyclooxygenase-1 activity, whereas tepoxalin administration resulted in inhibition of cyclooxygenase-1 and 5-lipoxygenase.

Effect of perzinfotel and a proprietary phospholipase A 2 inhibitor on kinetic gait and subjective lameness scores in dogs with sodium urate-induced synovitis

OBJECTIVE To investigate the ability of perzinfotel (an N-methyl-d-aspartate receptor antagonist) and a proprietary phospholipase A(2) (PLA(2)) inhibitor to attenuate lameness in dogs with sodium urate (SU)-induced synovitis. ANIMALS 8 adult dogs. PROCEDURES A blinded 4-way crossover study was performed. Dogs received perzinfotel (10 mg/kg), a proprietary PLA(2) inhibitor (10 mg/kg), carprofen (4.4 mg/kg; positive control treatment), or no treatment (negative control treatment). On the fourth day after initiation of treatment, synovitis was induced via intra-articular injection of SU 1 hour before administration of the last treatment dose. Ground reaction forces were measured and clinical lameness evaluations were performed before (baseline [time 0]) and 2, 4, 6, 8, 12, and 25 hours after SU injection. There was a 21-day washout period between subsequent treatments. Data were analyzed via repeated-measures ANOVAs. RESULTS Peak vertical force (PVF) and vertical impulse (VI) values for negative control and perzinfotel treatments were significantly lower at 2 and 4 hours, compared with baseline values. Values for PVF and VI for the PLA(2) inhibitor and positive control treatments did not differ from baseline values at any time points. Between-treatment comparisons revealed significantly higher PVF and VI values for the positive control treatment than for the negative control and perzinfotel treatments at 2 and 4 hours. Values for VI were higher for PLA(2) inhibitor treatment than for negative control treatment at 2 hours. CONCLUSIONS AND CLINICAL RELEVANCE Perzinfotel did not significantly alter SU-induced lameness. The proprietary PLA(2) inhibitor attenuated lameness but not as completely as did carprofen.