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Journal of Pharmacology and Experimental Therapeutics

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Abstract

Anti-inflammatory activity of BF389, a Di-T-butylphenol, in animal models of arthritis.

A M Bendele, D N Benslay, J T Hom, S M Spaethe, K J Ruterbories, T D Lindstrom, S J Lee and R W Naismith
Journal of Pharmacology and Experimental Therapeutics January 1992, 260 (1) 300-305;
A M Bendele
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D N Benslay
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J T Hom
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S M Spaethe
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K J Ruterbories
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T D Lindstrom
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S J Lee
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R W Naismith
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Abstract

Biofor 389 (BF389), dihydro-4-[[3,5-bis(1,1-dimethyl)-4-hydroxyphenyl] methylene]-2-methyl-2H-1,2-oxazin-3(4H)-one, was tested for anti-inflammatory activity in various animal models of arthritis. Initial evaluation in the lipoidalamine (LA) arthritis model in rats (5-day dosing protocol) resulted in an oral ED50 of 4.9 mg/kg for inhibition of paw swelling. No effects on splenomegaly were observed, suggesting that the compound was efficacious as a result of anti-inflammatory rather than immunomodulatory effects. BF389 was efficacious in interleukin 1 (IL-1)-enhanced type II collagen arthritis in rats (oral ED50 less than 1.0 mg/kg) as assessed by paw volume measurement and histologic evaluation of joints. Mice with IL-1-enhanced type II collagen arthritis given 30 mg/kg of BF 389 had significantly lower histological scores for joint damage than did untreated controls. Normal rats given single oral doses of BF389 had significant suppression of arachidonate-stimulated whole blood prostaglandin E2 and thromboxane B2 production 2 hr postdosing (ED50 = 0.1 mg/kg). Leukotriene B4 production in these animals was not decreased. After it became apparent that the compound was a potent inhibitor of prostaglandin production in vivo, a study was done to compare the efficacy and toxicity of BF389 with several currently marketed nonsteroidal anti-inflammatory drugs, piroxicam, naproxen and diclofenac. Lipoidalamine-injected rats were given daily oral doses of BF389 or the comparators for 21 days. Quantitation of effects on arthritis on day 21 resulted in ED50 values of 0.9 mg/kg (BF389), 3.9 mg/kg (naproxen), 4.9 mg/kg (diclofenac) and 0.6 mg/kg (piroxicam).(ABSTRACT TRUNCATED AT 250 WORDS)

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Journal of Pharmacology and Experimental Therapeutics
Vol. 260, Issue 1
1 Jan 1992
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Abstract

Anti-inflammatory activity of BF389, a Di-T-butylphenol, in animal models of arthritis.

A M Bendele, D N Benslay, J T Hom, S M Spaethe, K J Ruterbories, T D Lindstrom, S J Lee and R W Naismith
Journal of Pharmacology and Experimental Therapeutics January 1, 1992, 260 (1) 300-305;

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Abstract

Anti-inflammatory activity of BF389, a Di-T-butylphenol, in animal models of arthritis.

A M Bendele, D N Benslay, J T Hom, S M Spaethe, K J Ruterbories, T D Lindstrom, S J Lee and R W Naismith
Journal of Pharmacology and Experimental Therapeutics January 1, 1992, 260 (1) 300-305;
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