[Long-term toxicity of benorylate]

A long term study was carried out to determine the possible toxic effects of therapeutic doses of a suspension of benorilate on bone marrow, liver and kidneys in 33 patients with rheumatoid arthritis. 14 were male and 19 femal patients. 11 of the male and 14 of the female patients presented a positive rheumatoid factor. The duration of the treatment was first limited to 6 months. In 20 of the 33 patients duration of treatment was extended to 7 and 91/2 months. Three patients interrupted treatment after respectively 2, 3 and 5 months. Benorilate was given in a daily dosage varying from 6-8-12 g (as a suspension containing 40% benorilate). The following parameters were used to determine the effect of the drug on bone marrow: Hemoglobin, erythrocyte count, leucocyte count, thrombocyte count. Tests were done at regular intervals to determine a possible toxic effect on the kidney: urea nitrogen, uric acid, creatinine and urineanalysis were performed at regular intervals. To determine any possible hepatic toxicity, SGOT, SGPT, alkaline phosphatase and prothrombin time were done at regular intervals. On the basis of the laboratory results, no toxicity could be demonstrated in bone marrow, liver and kidneys when benorilate was given in therapeutic doses for the treatment of rheumatoid arthritis. Rare temporary abnormal laboratory values are not statistically significant and can be considered part of systemic involvement secondary to rheumatoid arthritis. The combination of the two active substances of benorilate decreases to a minimum on the one hand the above mentioned side effects and on the other potentiates the therapeutic and especially the analgetic effect. After resorption, the preparation is hydrolized in the plasma to acetylic salicylic acid and paracetamol. The hydrolysis takes place in the gastrointestinal tract which probably explains why the drug is so well tolerated.