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

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Abstract
Twelve rheumatic patients were given 2.0 and 4.5 g acetylsalicylic acid [ASA] daily in two 3 wk periods. On days 13 and 20 of each period the patients took a suppository containing 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 PG(prostaglandin)F2.alpha. release from platelets. The suppression of PGF2.alpha. release does not reflect the therapeutic response of the 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 2.0-4.5 g/day the unbound concentration increased 5-24 times. This reflects the combined effect of capacity-limited metabolism and capacity-limited protein binding of salicylate.