Dietary composition alters methotrexate toxicity without changing its pharmacokinetic parameters in cats

This study determined the effect of a commercial dry expanded (complex) diet and purified diet on methotrexate (MTX) toxicity and pharmacokinetics in the cat. Twelve cats were randomized to receive a purified diet or a complex diet for 21 days. They were then given an intravenous bolus injection of MTX at a dose of 10 mg/kg (160 mg/M²). Cats fed the purified diet had severe enteritis, characterized by depression, lethargy, diarrhea, and vomiting. Cats receiving the complex diet remained mentally bright, alert, and responsive throughout the post-chemotherapy period, and only one of six cats in this dietary group developed mild diarrhea 48 hr after MTX administration. Methotrexate was associated with a significant (P < 0.0001) reduction in the total white blood cell (WBC) counts in cats receiving the purified and complex diets. The elimination of MTX appeared to follow a three-compartment model of elimination. Plasma MTX concentrations at all time points examined were virtually identical in cats receiving the purified and complex diets. The terminal half-life of MTX in cats receiving the complex and purified diets was 1.75 ± 0.44 hr and 2.77 ± 0.8 hr, respectively. The similarity of plasma MTX concentrations and pharmacokinetic parameters in both dietary groups suggests that dietary alterations may influence enterotoxicity directly rather than altering exposure to MTX.