Potential long-term toxicity of repeated orally administered doses of artemether in rats.
Artemether, an efficacious antimalarial drug, effectively prevents patent schistosome infections and morbidity, as established in laboratory models and in clinical trials. In view of concern about the potential long-term toxicity, rats were treated orally with 80 mg/kg artemether once every 2 weeks for 5 months. After the final treatment, routine blood test results were normal except for reversible reductions of reticulocyte counts and reversible increases in hemoglobin levels. Liver and kidney function and histopathological examination showed no differences between treated and untreated rats. Administration of 400 mg/kg artemether resulted in transient focal vesicle degeneration of the liver or slight damage to the proprius layer lamina of intestinal villi. No damage to the central nervous system tissues, including cerebrum, cerebellum, midbrain, thalamus, pons, medulla oblongata, and spinal cord, was seen at either concentration. There were no alterations in electrocardiograms during the 6-month treatment period. We conclude that 80 mg/kg artemether administered once every 2 weeks is safe, and doses of 400 mg/kg do not result in evidence of neurotoxicology.
Institute of Parasitic Diseases, Chinese Academy of Preventive Medicine, Shanghai.
Shuhua
S
Xiao
Yuanqing
Y
Yang
Qiqing
Q
You
Jürg
J
Utzinger
Huifang
H
Guo
Jiao
J
Peiying
Jinying
J
Mei
Jian
J
Guo
Robert
R
Bergquist
Marcel
M
Tanner
D000284:Administration, Oral; D000818:Animals; D000962:Antimalarials / Q000008:administration & dosage / Q000633:toxicity*; D000077549:Artemether; D037621:Artemisinins; D001772:Blood Cell Count; D004562:Electrocardiography; D005260:Female; D006400:Hematocrit; D006454:Hemoglobins / Q000378:metabolism; D006651:Histocytochemistry; D007677:Kidney Function Tests; D008111:Liver Function Tests; D008137:Longitudinal Studies; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D012717:Sesquiterpenes / Q000008:administration & dosage / Q000633:toxicity*
D000962:Antimalarials; D037621:Artemisinins; D006454:Hemoglobins; D012717:Sesquiterpenes; D000077549:Artemether