Pharmacology and toxicology of diflunisal.

Abstract

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).

THE ORAL ACTIVITY OF Δ′‐TETRAHYDROCANNABINOL AND ITS DEPENDENCE ON PROSTAGLANDIN E2

“…but found no evidence for the presence of PGE, (Majerus & Stanford, 1977), whereas aspirin inhibits irreversibly by covalent acetylation of the cyclo-oxygenase (Roth, Stanford & Majerus, 1975). As an anti-inflammatory and analgesic compound, diflunisal is 7.5 to 13 times as active as aspirin in laboratory animals (Stone et al, 1977). However, in our experiments it is only about twice as effective as aspirin in reducing THC-induced catalepsy.…”

Characterization of a Francisella tularensis-Caenorhabditis elegans Pathosystem for the Evaluation of Therapeutic Compounds

“…Because diflunisal exhibited a lower MIC (8 g/ml) than mefloquine (16 g/ml) against F. tularensis LVS, we focused our further studies on the evaluation of diflunisal for its antibacterial activity and synergy with antibiotics. Moreover, the MIC (8 g/ml) of diflunisal is a lower dose than the plasma concentration of diflunisal (41 g/ml) required when it is used at the recommended dosage as an NSAID (40).…”

The effect of diflunisal on hyaluronic acid production by ‘activated’ human synovial fibroblasts.

“…Diflunisal was shown to possess both analgesic and anti-inflammatory properties (Stone et al, 1977). We have recently found it effective in the treatment of rheumatoid arthritis (Fishel et al, 1981).…”