Intravenous repeated-dose toxicity study of ZnPcS₂P₂-based-photodynamic therapy in beagle dogs

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• 作者：Wei Liu ; Naisheng Chen ; Hongtao Jin ; Jinling Huang ; Jinfeng Wei ; Jie Bao ; Chenghe Li ; Yan Liu ; Xueyong Li ; Aiping Wang
• 关键词：ZnPcS₂P₂ ; Photodynamic therapy (PDT) ; Repeated-dose toxicities ; Dogs ; Drug pigmentation ; Intravenous
• 刊名：Regulatory Toxicology and Pharmacology
• 出版年：2007
• 出版时间：April 2007
• 年：2007
• 卷：47
• 期：3
• 页码：221-231
• 全文大小：152 K

文摘

The purpose of current study was to investigate the potential repeated dosed toxicity of ZnPcP₂S₂-based photodynamic therapy (ZnPc-PDT) in Beagle dogs. Twenty-four Beagle dogs were randomly allocated to four groups, in which they were administered ZnPcS₂P₂ preparation intravenously at dosages of 0, 0.5, 1.5, and 4.5 mg/kg body weight and then were irradiated with 670 nm laser for 6 min at subsequent 48 and 72 h, once every four days for successively 10 times. There were no abnormal changes in clinical observations. After the administration most animals showed dysphoria and several had light edema on their faces. The results showed no mortality and no abnormity in ophthalmoscopy, electrocardiography, hematology, blood biochemistry and urinalysis, except that some statistical changes in specific indexes such as APTT in 1.5 and 4.5 mg/kg groups, and these changes disappeared at the end of recovery. Histopathological examination showed hepatic spotty and lytic necrosis in Beagle dogs of 4.5 mg/kg group, and at the end of recovery the damages alleviated. Additionally, some Kelly and Khaki granules presented in liver, spleen, lungs, kidneys, ovaries, lymph nodes, marrows and injection points. These drug pigmentations will provide valuable information about distribution of ZnPcP₂S₂. Based on the results; the NOAEL was considered to be 1.5 mg/kg and ZnPc-PDT appears to be a safety and promising approach in clinic.