Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:Q86TM3 (cage)
 29,987 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The anti-inflammatory effects of the non-steroidal anti-inflammatory drugs phenylbutazone (PBZ) and flunixin meglumine (FM) and the relationship between the effects and drug concentration in vivo were studied using a subcutaneous tissue-cage model in sheep. Intracaveal injection of carrageenan induced prostaglandin (PG) E2 production in tissue-cage exudate (maximal concentration, 101 nM) with significant increases in white blood cell (WBC) numbers, skin temperature over the inflamed cage and exudate leukotriene B4 (LTB4) concentration (P < 0.05). Intravenous PBZ, 4.4 mg kg-1 produced mild inhibition of exudate PGE2 generation (10%), but greater inhibition of serum TXB2 (75.3%). The IC50 for TXB2 was 36.0 microM. Phenylbutazone did not alter effects on skin temperature, WBC numbers or exudate LTB4 concentrations. Intravenous FM, 1.1 mg kg-1, significantly inhibited carrageenan-induced exudate PGE2 formation (Emax, 100%, IC50, < 0.4 nM) and serum TXB2 generation (Emax, 100%, IC50, 17 nM) for up to 32 h. Flunixin meglumine significantly inhibited the rise in skin temperature but had a limited effect on exudate WBC. Phenylbutazone and FM have distinct effects on carrageenan-induced cyclooxygenase (COX-2) and platelet COX (COX-1). Flunixin meglumine was a more potent COX inhibitor than PBZ and was more selective for the inducible form of COX in vivo.
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PMID:Measurement of cyclooxygenase inhibition in vivo: a study of two non-steroidal anti-inflammatory drugs in sheep. 967 7

Flunixin meglumine (FM, 1.1 mg/kg) and phenylbutazone (PBZ, 4.4 mg/kg) were administered intravenously (i.v.) as a single dose to eight sheep prepared with subcutaneous (s.c.) tissue-cages in which an acute inflammatory reaction was stimulated with carrageenan. Pharmacokinetics of FM, PBZ and its active metabolite oxyphenbutazone (OPBZ) in plasma, exudate and transudate were investigated. Plasma kinetics showed that FM had an elimination half-life (t1/2beta) of 2.48 +/- 0.12 h and an area under the concentration - time curve (AUC) of 30.61 +/- 3.41 Lg/mL x h. Elimination of PBZ from plasma was slow (t1/2beta = 17.92 +/- 1.74 h, AUC = 968.04 +/- microg/mL x h). Both FM and PBZ distributed well into exudate and transudate although penetration was slow, indicated by maximal drug concentration (Cmax) for FM of 1.82 +/- 0.22 microg/mL at 5.50 +/- 0.73 h (exudate) and 1.58 +/- 0.30 microg/mL at 8.00 h (transudate), and Cmax for PBZ of 22.32 +/- 1.29 microg/mL at 9.50 +/- 0.73 h (exudate) and 22.07 +/- 1.57 microg/mL at 11.50 +/- 1.92 h (transudate), and a high mean tissue-cage fluids:plasma AUClast ratio obtained in the FM and PBZ groups (80-98%). These values are higher than previous reports in horses and calves using the same or higher dose rates. Elimination of FM and PBZ from exudate and transudate was slower than from plasma. Consequently the drug concentrations in plasma were initially higher and subsequently lower than in exudate and transudate.
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PMID:Pharmacokinetic studies of flunixin meglumine and phenylbutazone in plasma, exudate and transudate in sheep. 973 55