Preclinical evaluation of L-asparaginase and methotrexate administered at intermediate doses in dogs.
The role of L-asparaginase (L-ASP) in limiting signs of methotrexate (MTX) toxicosis was studied. Eight dogs were randomly allotted to 2 groups of 4 dogs. All dogs were given 400 IU of L-ASP/kg of body weight IM, on day 1. On day 10, group-1 dogs were given 3 mg of MTX/kg, IV, and group-2 dogs were given 6 mg of MTX/kg, IV. All dogs were given 400 IU of L-ASP/kg, IM, 24 hours later (on day 11). One group-2 dog was euthanatized on day 16 because of severe gastrointestinal signs that were unresponsive to treatment. A second dose of MTX, identical to that given on day 10, was given on day 20 to each surviving dog, followed by L-ASP on day 21. On day 67, the 7 surviving dogs were given 3 mg of MTX/kg, IV. Adverse reactions observed were vomiting, diarrhea, and weight loss. Gastrointestinal side effects of MTX were not attenuated with L-ASP and would be a serious limitation to use of MTX administered at an intermediate dose in the treatment of lymphoma in dogs.
Bortnowski
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HB
Department of Medical Sciences, School of Veterinary Medicine, University of Wisconsin, Madison 53706.
Rosenthal
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RC
D000818:Animals; D001215:Asparaginase / Q000494:pharmacology* / Q000627:therapeutic use; D003967:Diarrhea / Q000139:chemically induced / Q000662:veterinary; D004283:Dog Diseases / Q000139:chemically induced* / Q000517:prevention & control; D004285:Dogs; D005260:Female; D008297:Male; D008727:Methotrexate / Q000037:antagonists & inhibitors / Q000633:toxicity*; D011897:Random Allocation; D014839:Vomiting / Q000139:chemically induced / Q000662:veterinary; D015431:Weight Loss / Q000187:drug effects
D001215:Asparaginase; D008727:Methotrexate