Intermediate-term toxicity of repeated orally administered doses of the anti-malarial beta-artemether in dogs.
The artemisinin derivative beta-artemether, an anti-malarial, was evaluated for its toxicity and tolerability in a 2-week, multiple-dose study in dogs. Eight beagle dogs (4 females, 4 males) were given beta-artemether by oral gavage 3 times daily at 45 mg/kg/dosing (a total daily dose-level of 135 mg/kg) for 2 weeks. This beta-artemether dose regime was well tolerated. Body weight changes were normal although feed consumption during the treatment period reduced compared to that of the pre-trial period. Clinical signs were transient spells of soft to liquid feces. On completion of the treatment period, the animals were sacrificed and submitted to a full macroscopic post-mortem examination. Designated organs were weighed and a complete light microscopic examination was performed on 43 selected tissues from 1 animal per sex, and on the liver, kidneys, thymus, mandibular lymph nodes and lungs of the three other animals per sex. Major findings were high liver weight and histopathologic findings of slight diffuse hepatocellular hypertrophy and distal tubular dilatation, together with flattened epithelium, in the kidneys. With the dose regime used in this trial beta-artemether produced no clinical or apparent histopathological signs of neurotoxicity in dogs.
Peys
Eric
E
Kemin Pharma, R&D Department, Atealaan 4H, 2200 Herentals, Belgium. eric.peys@kemin.com
Vandenkerckhove
Jan
J
Van Hemel
Johan
J
Sas
Benedikt
B
D000284:Administration, Oral; D000818:Animals; D000962:Antimalarials / Q000633:toxicity*; D000077549:Artemether; D037621:Artemisinins / Q000633:toxicity*; D049108:Cell Enlargement / Q000187:drug effects; D004285:Dogs; D004435:Eating / Q000187:drug effects; D004847:Epithelial Cells / Q000187:drug effects / Q000473:pathology; D005260:Female; D022781:Hepatocytes / Q000187:drug effects / Q000473:pathology; D006984:Hypertrophy / Q000139:chemically induced / Q000473:pathology; D007686:Kidney Tubules, Distal / Q000187:drug effects / Q000473:pathology; D008099:Liver / Q000187:drug effects / Q000473:pathology; D008297:Male; D009929:Organ Size / Q000187:drug effects; D018675:Toxicity Tests
D000962:Antimalarials; D037621:Artemisinins; D000077549:Artemether