Methotrexate-nonsteroidal antiinflammatory drug interaction in children with arthritis

In order to assess the interaction between methotrexate (MTX) and nonsteroidal antiinflammatory drugs (NSAID), we studied the pharmacokinetics of oral MTX alone and in the presence of the usually prescribed NSAID in 7 children with chronic arthritis. The NSAID studied included tolmetin, indomethacin, naproxen, and aspirin. Six patients were treated with multiple NSAID. The mean MTX elimination half-life was prolonged when NSAID were coadministered (1.7 +/- 0.5 vs 1.2 +/- 0.1 h; p = 0.03). However, neither the apparent MTX clearance (CI) (10.6 +/- 5.5 vs 13.1 +/- 3.5 l/h; p = 0.19), the area under the serum MTX concentration-time curve (Auc) (2.1 +/- 1.0 vs 1.5 +/- 0.6 mumol/l/h; p = 0.08) or the apparent volume of distribution (Vd) (23.0 +/- 6.2 vs 21.9 +/- 6.4 l; p = 0.53) was significantly altered by the administration of NSAID. Although the differences between the mean Cl and Auc were not statistically significant, a wide variation in the impact of NSAID on MTX Cl was observed. In 6 of 7 patients, the Auc increased during NSAID administration from 19 to 140%. This degree of increase may be clinically significant in some individuals. It is consequently recommended to closely monitor patients who are receiving MTX and NSAID for MTX toxicity until these results can be verified in a larger population.