EQUIANALGESIC EFFECTS OF PARACETAMOL AND INDOMETHACIN IN RHEUMATOID ARTHRITIS

The therapeutic and adverse effects of 2 weeks of treatmentwith high-dose indomethacin (150 mg/day) were compared withthose of low-dose indomethacin (50 mg/day) combined with paracetamol(4 g/day) in a double-blind, double-dummy, cross-over studyin 17 patients with active rheumatoid arthritis. Grip strength,Ritchie's index, joint circumference, joint pain, and patient'sand physician's global assessments were estimated, and conventionallaboratory parameters were followed. In addition, the time-concentrationprofiles of indomethacin and paracetamol were assessed duringsteady state. All patients had measurable plasma drug levels,indicating adequate compliance, and responders and nonresponders(five on each treatment) had equal drug levels, indicating thatthe variation in therapeutic efficacy was not secondary to pharmacokineticdifferences. While there were fewer and milder side-effectsduring treatment with the drug combination, there was no differencein therapeutic efficacy. Hence, it appears that the main therapeuticprofit of indomethacin in daily doses greater than 50 mg isenhanced analgesia. As such dosage involves pronounced side-effects,it seems more appropriate to employ the combination of 50 mgindomethacin and 4 g paracetamol, whereby similar analgesiacan be obtained without an increase in side-effects. KEY WORDS: Rheumatoid arthritis, Analgesia, Paracetamol, Indomethacin, Plasma levels.