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Etodolac was compared with aspirin and placebo for efficacy and safety, and a minimum effective dose was established in 264 patients with adult-onset, active rheumatoid arthritis. In this six-week, 14-center, double-blind, parallel-group investigation, preceded by a washout period of up to two weeks, patients received daily doses of etodolac at 50, 100, or 200 mg/d; aspirin at 3,900 mg/d; or placebo. Both etodolac at the highest dose and aspirin produced statistically significant improvement from baseline in all disease activity assessments measured at four- and six-week end points and were superior to placebo in the majority of assessments. A greater number of patient complaints occurred with aspirin, especially in regard to gastrointestinal-related and otologic side effects. A significant therapeutic dose response was evident among the etodolac groups without an increase in side effects. Although the 100-mg/d dose was effective in many of the efficacy parameters measured, the 200-mg/d dose, which is comparably efficacious to aspirin 3.9 g/d, was suggested as the minimum effective dose for the relief of the signs and symptoms of active rheumatoid arthritis.

Etodolac, a nonsteroidal antiinflammatory and analgesic drug, was used in a randomized, parallel group, open-label design study, with stool analysis conducted in a blind fashion, to compare its effect in normal men in doses of 400 mg (N = 11) and 600 mg (N = 12) b.i.d. on gastrointestinal microbleeding with that of 600 mg ibuprofen, q.i.d. (N = 12), 50 mg indomethacin in the morning, 50 mg at noon, and 100 mg h.s. (N = 9), and 375 mg naproxen b.i.d. (N = 9). Etodolac was given at about 2 1/2 and 3 1/2 times the mean effective dose used for treating patients with rheumatoid arthritis. The other drugs were given at their manufacturers' maximum recommended doses. Lead-in placebo was given for one week, active drug for one week, and washout placebo for one week. Fecal blood loss was measured by the 51Cr-tagged red cell method, and was averaged over days 4-7 (baseline), 11-14 (treatment period), and 17-20 (washout). The mean increase in blood loss for the treatment period for the 400 mg etodolac b.i.d. group (0.13 ml) and 600 mg etodolac b.i.d. group (0.10 ml) was significantly less (P = 0.001) than the corresponding values for ibuprofen (1.14 ml), indomethacin (1.20 ml), and naproxen (0.87 ml). There was no tendency for greater blood loss at higher doses of etodolac. Etodolac at doses in excess of the mean effective dose in osteoarthritis and rheumatoid arthritis caused significantly less microbleeding in normal male volunteers during the seven-day treatment period than the other drugs tested, and not clinically more than that occurring during baseline placebo.

Twenty subjects (10 with normal renal function and 10 with moderate renal insufficiency) participated in an 8-day study to assess the effects of acute and chronic etodolac dosing on renal function. Subjects and patients were hospitalized and followed a controlled diet (150 mEq sodium, 60 to 80 mEq potassium) during the study. A 3-day drug-free period was followed by 4 days of etodolac, 200 mg b.i.d. Sodium balance and body weight remained unchanged in both groups. Modest reductions in renal function as measured by clearances of inulin and p-aminohippurate occurred acutely only in the patients with renal impairment. Chronic therapy resulted in no decrements in daily creatinine clearance. In an average effective anti-inflammatory dose, etodolac did not produce a sustained effect on renal function in either normal subjects or patients with moderate renal insufficiency.