Intravenous repeated-dose toxicity study of ZnPcS2P2-based-photodynamic therapy in beagle dogs.
The purpose of current study was to investigate the potential repeated dosed toxicity of ZnPcP(2)S(2)-based photodynamic therapy (ZnPc-PDT) in Beagle dogs. Twenty-four Beagle dogs were randomly allocated to four groups, in which they were administered ZnPcS(2)P(2) preparation intravenously at dosages of 0, 0.5, 1.5, and 4.5mg/kg body weight and then were irradiated with 670nm laser for 6min at subsequent 48 and 72h, 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 4.5mg/kg groups, and these changes disappeared at the end of recovery. Histopathological examination showed hepatic spotty and lytic necrosis in Beagle dogs of 4.5mg/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 ZnPcP(2)S(2). Based on the results; the NOAEL was considered to be 1.5mg/kg and ZnPc-PDT appears to be a safety and promising approach in clinic.
Liu
Wei
W
New Drugs Safety Evaluation Center, Institute of Materia Medica, Peking Union Medical College, China.
Chen
Naisheng
N
Jin
Hongtao
H
Huang
Jinling
J
Wei
Jinfeng
J
Bao
Jie
J
Li
Chenghe
C
Liu
Yan
Y
Li
Xueyong
X
Wang
Aiping
A
D000818:Animals; D004285:Dogs; D005260:Female; D007211:Indoles / Q000633:toxicity*; D007275:Injections, Intravenous; D007834:Lasers; D008099:Liver / Q000187:drug effects / Q000473:pathology; D008297:Male; D019055:No-Observed-Adverse-Effect Level; D009942:Organometallic Compounds / Q000633:toxicity*; D010314:Partial Thromboplastin Time; D010778:Photochemotherapy; D017319:Photosensitizing Agents / Q000633:toxicity*
D007211:Indoles; D009942:Organometallic Compounds; D017319:Photosensitizing Agents; C064329:zinc phthalocyanine disulfonate