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

• Published in: The Journal of nutritional biochemistry 1997-02, Vol.8 (2), p.79-84
• Main Authors: Marks, Stanley L., Vulliet, P.Richard, Kass, Philip H., Rogers, Quinton R.
• Format: Article
• Language: English
• Subjects: ACIDE AMINE; AMINO ACIDS; AMINOACIDOS; ANIMAL MODELS; ANTIVITAMINAS; ANTIVITAMINE; ANTIVITAMINS; Biological and medical sciences; BLOOD CELLS; BLOOD PLASMA; cat; CATS; CELLULE SANGUINE; CELULAS SANGUINEAS; CHAT; DIET; DIETA; ENTERITE; ENTERITIS; FARMACOLOGIA; feline; Gastroenterology. Liver. Pancreas. Abdomen; GATO; HALF LIFE; LEUCOCITOS; LEUCOCYTE; LEUKOCYTES; Medical sciences; methotrexate pharmacokinetics; MODELE ANIMAL; MODELOS ANIMALES; Other diseases. Semiology; PHARMACOLOGIE; PHARMACOLOGY; PLASMA SANGUIN; PLASMA SANGUINEO; purified diet; REGIME ALIMENTAIRE; SINTOMAS; Stomach. Duodenum. Small intestine. Colon. Rectum. Anus; SYMPTOME; SYMPTOMS; TOXICIDAD; TOXICITE; TOXICITY
• ISSN: 0955-2863; 1873-4847
• DOI: 10.1016/S0955-2863(96)00177-5

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/M 2). 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.