著者

Fukiko MATSUYAMA Yukiyoshi FUJITA Eri FUKAZAWA Tetsuya KOBAYASHI

出版者

JAPANESE SOCIETY OF VETERINARY SCIENCE

雑誌

Journal of Veterinary Medical Science (ISSN:09167250)

巻号頁・発行日

pp.23-0200, (Released:2023-10-10)

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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.