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Cotton pellet‐induced granuloma formation in intact animals is intimately dependent upon body growth and general anabolic processes. Deposition of connective tissue around the pellet continues up to (and probably beyond) the observation period of 90 days after implantation. Anorexic or catabolic agents, or both, or restricted food intake markedly impairs granuloma formation as a result of an impaired body growth. By expressing the amount of granuloma formed in mg/100 g body weight, the true anti‐granulomatous properties of a drug can be easily dissociated from those attributable to an impaired body growth. The mechanism by which impairment in body growth affects granuloma formation is discussed.

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A novel series of antiinflammatory agents, N-isoxazolyl-3-carboxamides of 4-hydroxy-2H-1,2-benzothiazine 1,1-dioxide, was synthesized and evaluated as antiinflammatory agents in the carrageenin-induced rat paw edema (CIRPE) assay and adjuvant-induced polyarthritis (AIP) assay. Several analogues were found to be equipotent or more potent than aspirin and phenylbutazone. Structure-activity relationships are discussed. One of the compounds, 4-hydroxy-2-methyl-N-(5-methyl-3-isoxazolyl)-2H-1,2-benzothiazine 3-carboxamide 1,1-dioxide (3a; isoxicam), was found to be 3 times as potent as phenylbutazone in the CIRPE and in the therapeutic AIP assays. Isoxicam (3a) is presently undergoing phase III clinical trial as an antiarthritic drug.

Isoxicam is a potent, orally active, nonsteroidal anti-inflammarory drug with prolonged activtiy in experimentally induced inflammation in rats. Isoxicam is less ulcerogenic, acutely less toxic and, therefore, appears to have a therapeutic ratio superior to other standard agents to which it was compared.