We have compared the effect of single and multiple doses of indomethacin and placebo on objective measurements of psychomotor impairment in patients. Following a single 50 mg dose (n = 8), indomethacin produced psychomotor disturbance in only those patients who had no recent history of NSAID exposure. After multiple doses of indomethacin (25 and 50 mg tid for 5 days), significant psychomotor impairment was observed. We conclude that other NSAIDs may induce cross-tolerance to the psychomotor effects of indomethacin. Tachyphylaxis may develop to the psychomotor disturbance caused by indomethacin.

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The effect of 5 days treatment with allopurinol (300mg) on the pharmacokinetics of indomethacin at steady-state was investigated in eight patients. Allopurinol produced no significant effect on the indomethacin serum concentration-time curve. Allopurinol did not alter significantly the amounts of indomethacin excreted in the urine within 8 h. However, the urinary ratio of N-deschlorobenzoylindomethacin to indomethacin was reduced significantly by allopurinol administration (P < 0.05).

No abstract