1 Diflunisal, a new salicylate, possesses anti-inflammatory, analgesic and antipyretic activity. It was found to be about 7.5-13 times more active than aspirin as an analgesic (Randall-Selitto assay in rats) and as an anti-inflammatory agent (carrageenin foot oedema and adjuvant arthritis in rats). 2 Diflunisal was 1.4 times as active as aspirin as an antipyretic in the rat and about three times as potent in reducing lameness induced by injecting urate crystals into the knee joint of dogs. 3 Diflunisal inhibited adenosine diphosphate, adrenaline and thrombin-induced aggregation of human platelets in vitro. The concentrations required were 18-35 times higher than those needed with aspirin.4 After single doses, both diflunisal and aspirin induced gastric haemorrhages in starved rats. This was evident only after relatively large doses of diflunisal, whereas aspirin induced gastric changes after pharmacologically active amounts. 5 Diflunisal, but not aspirin, after single doses, produced perforations of the small intestine in the rat. The dose levels required were considerably above those that would demonstrate anti-inflammatory and analgesic activity. 6 In oral subacute toxicity studies in rats and dogs of 14 weeks' duration, diflunisal and aspirin produced similar gastric and renal toxicity. Both produced focal oedema, haemorrhage and small ulcers in one or both species. Renal changes were limited to a slight degree of oedema of the papilla in the rat and dog. Diflunisal, but not aspirin, produced intestinal lesions of the small bowel in the rat but not the dog. The changes with either drug were largely limited to the higher levels used (50-200 mg/kg/d).

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