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Measurement of Cyclooxygenase Inhibition in vivo: A Study of Two Non-Steroidal Anti-Inflammatory Drugs in Sheep

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Abstract

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) E2production 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 μM. 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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Authors and Affiliations

  1. Division of Veterinary Pharmacology, Department of Veterinary Preclinical Studies, University of Glasgow, Bearsden Road, Glasgow, G61 1QH, UK. Present address: Department of Veterinary Basic Sciences, Royal Veterinary College, Bolton's Park, 44 Hawkshead Road, Potters Bar, Herts, UK

    Z. Cheng, A. M. Nolan & Q. A. McKellar

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  2. A. M. Nolan
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  3. Q. A. McKellar
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Cheng, Z., Nolan, A.M. & McKellar, Q.A. Measurement of Cyclooxygenase Inhibition in vivo: A Study of Two Non-Steroidal Anti-Inflammatory Drugs in Sheep. Inflammation 22, 353–366 (1998). https://doi.org/10.1023/A:1022364731126

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