Co-
artemether is a fixed combination tablet comprising one part of artemether and six parts of benflumetol (1∶6, W/W). Experiments were carried out in
beagle dogs. The dogs were divided randomly into groups of defferent
dose (112, 556, 1000 mg·kg -1·d -1) and blank control group. Each group consisted of 3 males and 3 females. The drug was given once daily for 14 successive days. Manifestations and behaviors of the dogs, hematology, blood chemistry, urinalysis, electrocardiogram(ECG), ophthalmoscopy, necropsy and histopathology were examined. Twenty-four hours after the last dose, 4 dogs of each group were sacnificed and the others in each group were remained to be further observed for four weeks. The experiment suggested that the most sensitive tissue in the toxic effects induced by oral administration of co-artemether be still the
erythrocytic system of bone
marrow as was the case for injection of artemisinin derivatives. The reticulocyte count and the ratio of polychromatic
normoblast/basophilic normoblast of erythrocytic series of bone marrow tended to decrease in 1000 mg·kg -1·d -1 group. In addition, prolongation of Q-T interval of ECG and transient increase in GOT and alkaline phosphatase activity were also observed. Histological examination revealed mild tissue damage of liver and kidney. All of these changes were reversible after stopping treatment. The dose 556 mg·kg -1·d -1 (50 times as large as the dose to be used in man) was considered as practically safe dose.
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