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

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3 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)79-84
Number of pages6
JournalJournal of Nutritional Biochemistry
Volume8
Issue number2
DOIs
StatePublished - Feb 1997

Fingerprint

Pharmacokinetics
Nutrition
Methotrexate
Toxicity
Cats
Diet
Chemical analysis
Diarrhea
Plasmas
Lethargy
Chemotherapy
Enteritis
Leukocyte Count
Intravenous Injections
Vomiting
Half-Life
Blood
Cells
Depression
Drug Therapy

Keywords

  • cat
  • enteritis
  • feline
  • methotrexate pharmacokinetics
  • purified diet

ASJC Scopus subject areas

  • Biochemistry
  • Endocrinology, Diabetes and Metabolism

Cite this

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title = "Dietary composition alters methotrexate toxicity without changing its pharmacokinetic parameters in cats",
abstract = "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.",
keywords = "cat, enteritis, feline, methotrexate pharmacokinetics, purified diet",
author = "Marks, {Stanley L} and Vulliet, {Philip R} and Kass, {Philip H} and Quinton Rogers",
year = "1997",
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AU - Marks, Stanley L

AU - Vulliet, Philip R

AU - Kass, Philip H

AU - Rogers, Quinton

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N2 - 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.

AB - 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.

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