Preclinical evaluation of L-asparaginase and methotrexate administered at intermediate doses in dogs.

Abstract

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.

• Authors: H B Bortnowski, R C Rosenthal
• Journal: American journal of veterinary research (Am J Vet Res) Vol. 52 Issue 10 Pg. 1636-8 (Oct 1991) ISSN: 0002-9645 [Print] United States
• PMID: 1767984 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Asparaginase
• Methotrexate

Topics

• Animals
• Asparaginase (pharmacology, therapeutic use)
• Diarrhea (chemically induced, veterinary)
• Dog Diseases (chemically induced, prevention & control)
• Dogs
• Female
• Male
• Methotrexate (antagonists & inhibitors, toxicity)
• Random Allocation
• Vomiting (chemically induced, veterinary)
• Weight Loss (drug effects)