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.


METHODS
8 healthy adult male cats.


METHODS
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
Firocoxib and meloxicam administration had no effect on cyclooxygenase-1 activity, whereas tepoxalin administration resulted in inhibition of cyclooxygenase-1 and 5-lipoxygenase.
Goodman
Laura A
LA
Department of Small Animal Medicine and Surgery, College of Veterinary Medicine, University of Georgia, Athens, GA 30602, USA. lgoodman@uga.edu
Torres
Bryan T
BT
Reynolds
Lisa R
LR
Budsberg
Steven C
SC
D015107:4-Butyrolactone / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000097:blood / Q000494:pharmacology; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000494:pharmacology; D002415:Cats; D018592:Cross-Over Studies; D016861:Cyclooxygenase Inhibitors / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology*; D015232:Dinoprostone / Q000378:metabolism; D004386:Duodenum / Q000187:drug effects / Q000502:physiology; D015777:Eicosanoids / Q000096:biosynthesis*; D005753:Gastric Mucosa / Q000187:drug effects / Q000378:metabolism; D007413:Intestinal Mucosa / Q000187:drug effects / Q000378:metabolism; D007700:Kinetics; D007975:Leukotriene B4 / Q000378:metabolism; D008297:Male; D000077239:Meloxicam; D009919:Orchiectomy; D011720:Pyrazoles / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology*; D012016:Reference Values; D013450:Sulfones / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology*; D013843:Thiazines / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology*; D013844:Thiazoles / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology*
D000894:Anti-Inflammatory Agents, Non-Steroidal; D016861:Cyclooxygenase Inhibitors; D015777:Eicosanoids; D011720:Pyrazoles; D013450:Sulfones; D013843:Thiazines; D013844:Thiazoles; D007975:Leukotriene B4; D015232:Dinoprostone; D015107:4-Butyrolactone; C073135:tepoxalin; D000077239:Meloxicam; C487384:firocoxib