Master of Science / Department of Clinical Sciences / Elizabeth Davis / The first aim of the current study was to investigate the pharmacokinetics of oral meloxicam tablets and the gastrointestinal and renal effects after a 14-day treatment period. Meloxicam was orally administered to six adult horses once daily at a dosage of 0.6 mg/kg for 14 consecutive days. Blood was collected prior to each administration and at 20 and 40 min, and 1, 2, 4, 8, 12, and 24 hours after administration on days 1, 7, and 14 for the determination of meloxicam plasma concentrations by mass spectrometry. In addition, trough samples were taken on days 3 and 10. Complete blood count, serum biochemical analysis, urinalysis, and gastroscopy were performed at baseline and conclusion of the investigation.
Complete blood count, serum chemistry, and urinalysis results were unchanged through the study period. Gastroscopy scores were not significantly increased. The Cmax was 1.82 ± 0.80 µg/mL at Tmax 3.48 ± 3.30 hr on day 1, 2.07 ± 0.94 µg/mL at Tmax 1.24 ± 1.24 hr on day 7, and 1.81 ± 0.76 µg/mL at 1.93 ± 1.30 h on day 14 (p = 0.30). The mean half-life was 4.99 ± 1.11 h.
The second aim of the study was to compare the analgesic effects and gastrointestinal and renal adverse effects of oral meloxicam tablets (0.6 mg/kg) to oral phenylbutazone tablets (4.4 mg/kg) orally once daily for 4 days in induced and naturally occurring lameness in adult horses. The study was performed on 4 healthy but lame adult horses. Complete blood count, serum biochemistry, urinalysis, and gastroscopy were performed prior to entrance to the study. Lameness was exacerbated in two horses using lipopolysaccharide (LPS; E. coli O55:B5) injected into the right metacarpophalangeal joint. The remaining two horses had Grade 3 or Grade 4 lameness due to naturally occurring laminitis. Meloxicam or phenylbutazone was administered to two horses each in a blinded, randomized manner once daily for four days. Lameness was evaluated using a pressure mat system and contact pressure, force, and stride length were evaluated at baseline and twice daily.
Complete blood count, serum chemistry, and urinalysis were unremarkable for all four horses except one horse with an increased GGT. This horse experienced hepatic rupture secondary to amyloidosis the final day of the study. Gastric ulcer scores did not change during the study period. Phenylbutazone administration resulted in a greater response (force and contact area) in the right front and left hind limbs compared to meloxicam administration. There were not enough data points to evaluate the other two limbs.
A third aim of the study was two-fold and first evaluated the effects of ex vivo stimulation of peripheral blood mononuclear cells (PBMCs) with LPS on cyclooxygenase (COX) messenger RNA (mRNA) expression. The second portion documented the effects of LPS-induced joint inflammation and treatment with non-steroidal anti-inflammatory drugs on the mRNA and protein expression of COX-2 in PBMCs. The results indicate that LPS upregulates COX-2 gene expression in PBMCs. Additionally, injection of LPS into the metacarpophalangeal joint increases both COX-2 mRNA and protein expression in PBMCs at 24 hours after injection. The relative expression of COX-2 after treatment with meloxicam or phenylbutazone indicates a stronger inhibition with phenylbutazone; however, further study with additional horses is needed.
Pharmacokinetic analysis of the oral tablet formulation of meloxicam indicates the pharmacokinetics are similar to the oral suspension formulation. Meloxicam appears to be inferior to phenylbutazone in its analgesic properties for induced lameness and naturally occurring laminitis, however the small sample size used in the study makes interpretation difficult.
| Identifer | oai:union.ndltd.org:KSU/oai:krex.k-state.edu:2097/15314 |
| Date | January 1900 |
| Creators | Vander Werf, Karie |
| Publisher | Kansas State University |
| Source Sets | K-State Research Exchange |
| Language | en_US |
| Detected Language | English |
| Type | Thesis |
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