The effect of 10 alpha-trifluoromethylhydroartemisinin on Plasmodium berghei infection and its toxicity in experimental animals.
The antimalarial activity of 10 alpha-trifluoromethylhydroartemisinin (TFMHA) was compared to that of dihydroartemisinin (DHA) in the Plamodium berghei mouse model. Treatment with TFMHA in mice infected with a P. berghei chloroquine-sensitive strain at 25 mg/kg for 3, 5, and 7 d, or DHA at the same dose for 7 d showed the parasite was eliminated from the host within 2.6 d. The radical cure and survival rates of these mice up to 60 d after infection were 90-100%. In mice infected with the P. berghei chloroquine-resistant strain, TFMHA used at 25 mg/kg/day for 3, 5, or 7 d reduced parasitaemia within 2 d. The radical cure and survival rates of these animals up to 60 d after infection were 30, 60, and 90% for the 3 treatment durations respectively. In contrast, DHA only had an inhibitory effect on the growth of the parasite within the first few days of treatment and could not eliminate the parasite even after 7 d of treatment. There was a 100% relapse and all mice died within 28 d after infection. The acute toxicity of TFMHA as determined by the median lethal dose (LD50) in mice treated orally was 820 mg/kg. In rabbits, TFMHA given orally at 20 mg/kg once daily for 28 successive days had no effect on the bodyweight, haematological, biochemical, histopathological and electrocardiogram parameters. The results showed that TFMHA is an effective antimalarial drug with a low level of toxicity.
Binh
Phan Dang
PD
Research and Malaria Treatment Laboratory, National Institute of Malariology, Parasitology and Entomology (NIMPE), Ha Noi, Viet Nam. bhang@netnam.vn
Cong
Le Dinh
le D
Nhu
Truong Van
TV
Tien
Nong Thi
NT
Nhan
Doan Hanh
DH
Bégué
Jean-Pierre
JP
Bonnet-Delpon
Danièle
D
Thanh Nga
Truong Thi
TT
D000818:Animals; D000962:Antimalarials / Q000627:therapeutic use; D037621:Artemisinins / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D004353:Drug Evaluation, Preclinical; D004351:Drug Resistance; D006339:Heart Rate / Q000187:drug effects; D007783:Lactones / Q000627:therapeutic use; D008288:Malaria / Q000188:drug therapy*; D051379:Mice; D018512:Parasitemia / Q000188:drug therapy; D010962:Plasmodium berghei / Q000187:drug effects*; D011817:Rabbits; D012717:Sesquiterpenes / Q000627:therapeutic use* / Q000633:toxicity; D016019:Survival Analysis
C454480:10-trifluoromethylanhydrodihydroartemisinin; D000962:Antimalarials; D037621:Artemisinins; D007783:Lactones; D012717:Sesquiterpenes; C039060:artenimol; C075875:artemisin