Effect of indomethacin on the pharmacokinetics of methotrexate in rabbits.
The interaction between indomethacin (IND) and methotrexate (MTX) was investigated in rabbits. The study was designed so as to evaluate the effect of IND (1 mg h-1) during a continuous MTX infusion (1 x 2 mg kg-1) over 240 min. IND was injected i.v. at hourly intervals after a steady state MTX concentration had been established. Plasma MTX concentration before and after IND did not differ significantly (p greater than 0.05). The elimination half-life (t1/2 beta) calculated during the washout interval (mean +/- SD) was 47 x 4 +/- 21 x 5 min which is close to that calculated in a reference group of rabbits. This excludes the possibility of delayed elimination as responsible for this toxicity. The toxicity of this combination was confirmed despite the absence of significant pharmacokinetic changes. It is possible that the toxic interaction was caused by enhanced cytotoxic effect of MTX.
Najjar
T A
TA
Department of Clinical Pharmacy, College of Pharmacy, King Saud University, Riyad, Saudi Arabia.
Morad
A R
AR
Khan
R M
RM
D000818:Animals; D004347:Drug Interactions; D007213:Indomethacin / Q000494:pharmacology*; D008297:Male; D008657:Metabolic Clearance Rate / Q000187:drug effects; D008727:Methotrexate / Q000097:blood / Q000493:pharmacokinetics*; D011817:Rabbits
D007213:Indomethacin; D008727:Methotrexate