Hosny A. Elewaa, Rowaida Refaat*b, Zeinab Alkasaby Zalatc
Methotrexate (MTX), a disease modifying antirheumatic drug (DMARD), and indomethacin, a non-steroidal anti-inflammatory drug (NSAID), are usually prescribed concomitantly for treatment of rheumatoid arthritis. The study aimed at investigating the effect of co-administration of indomethacin on the pharmacokinetics of MTX. Six female New Zealand rabbits (Group I) received MTX (10 mg/kg IV, once weekly). Six more animals (Group II) were treated concomitantly with MTX (10 mg/kg IV, once weekly) and indomethacin (4 mg/kg IV, once daily). Plasma levels of MTX were determined at 24, 36, 48, 60, 72, 96, and 120 hr after dosing during first, second, and third weeks. Concomitant administration of indomethacin significantly altered the studied pharmacokinetic parameters of MTX. The mean half life of MTX of about 13 hr in Group I gradually increased in Group II to 34.3 hr by the end of treatment. This was accompanied by 1.5-fold increase in the area under plasma concentration time curve (AUC). The total body clearance of MTX significantly decreased by 63.6%, while its mean residence time increased by about 1.43 fold during third week. In conclusion, the concurrent use of indomethacin with MTX caused significant changes in MTX pharmacokinetics and therefore care must be given in such situations.
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