Additive Clinical Effect of Indomethacin Suppositories During Salicylate Therapy in Rheumatoid Patients

Abstract

Twelve rheumatic patients were given 2.0 and 4.5 g acetylsalicylic add daily in two 3-week periods. On days 13 and 20 of each period the patients took a suppository containing either placebo or 50 mg of indomethacin. The study was performed double-blind. Indomethacin had a significant additive effect during ASA therapy with 2 g daily as estimated by articular index and subjective ratings of pain and morning stiffness. On the 4.5 g ASA dose there was a significant improvement only for articular index. The patients experienced less pain during maintenance therapy with 4.5 g of ASA compared with 2.0 g daily. Both ASA doses induced complete inhibition of prostaglandin PGF_2α release from platelets. Thus the suppression of PGF_2α release does not reflect the therapeutic response of these drugs. Side effects observed comprised tinnitus, dizziness and gastritis. In 2 of the patients the aminotransferase levels increased, indicating hepatotoxicity. The protein binding of salicylate decreased with increasing salicylate concentration. As the dose was increased from 2.0 to 4.5 g/day the unbound concentration increased 5 to 24 times. This reflects the combined effect of capacity-limited metabolism and capacity-limited protein binding of salicylate.