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Safety and pharmacokinetics of thalidomide in tumor-bearing dogs.

Authors
  • Matsuyama, Fukiko1
  • Fujita, Yukiyoshi2
  • Fukazawa, Eri1
  • Kobayashi, Tetsuya1
  • 1 Japan Small Animal Cancer Center, Saitama, Japan. , (Japan)
  • 2 Gunma Prefectural Cancer Center, Gunma, Japan. , (Japan)
Type
Published Article
Journal
The Journal of veterinary medical science
Publication Date
Dec 06, 2023
Volume
85
Issue
12
Pages
1261–1268
Identifiers
DOI: 10.1292/jvms.23-0200
PMID: 37813647
Source
Medline
Keywords
Language
English
License
Unknown

Abstract

Thalidomide, an angiogenesis inhibitor, has recently been used to treat malignant canine tumors. This study retrospectively investigated the adverse events (AEs) of thalidomide administered to tumor-bearing dogs. We investigated the pharmacokinetics of thalidomide after administration and the rate of body weight change before and after administration. The initial thalidomide dose was 5 mg/kg per os once daily, which was increased to 10 mg/kg once daily in dogs with no significant AEs. Pharmacokinetics were measured in four dogs after the 5 mg/kg or 10 mg/kg dose. We evaluated AEs related to clinical signs in 51 patients; 9/51 had lethargy, 6/51 had tremor, 4/51 had dizziness, 31/51 had decreased appetite, 8/51 had vomiting, and 16/49 had soft stool/diarrhea. We evaluated hematologic toxicity in 44 patients with grade 3 or higher adverse events; 1/44 had thrombocytopenia, 1/44 had increased blood urea nitrogen concentrations, and 5/44 had increased alanine aminotransferase activities. The mean thalidomide blood levels were Cmax=1.4 ± 0.7 μg/mL (Area under the curve [AUC]0-24=8.5 ± 4.7 μg•hr /mL) and Cmax=3.2 ± 2.1 μg/mL (AUC0-24=22.0 ± 14.7 μg•hr/mL) in the 5 mg/kg and 10 mg/kg groups, respectively. The Cmax and AUC in the 10 mg/kg group were comparable to the effective blood concentrations seen in humans administered thalidomide. The weight fluctuation rates were assessed in 24 dogs approximately 1 month after the start of thalidomide administration; more than half showed weight maintenance or gain. Most AEs were clinically acceptable; however, peripheral nerve signs were seen in some dogs.

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