Risk assessment and therapeutic indices of artesunate and artelinate in Plasmodium berghei-infected and uninfected rats.
Int J Toxicol
; 24(4): 251-64, 2005.
Article
en En
| MEDLINE
| ID: mdl-16126619
ABSTRACT
Artesunate (AS) is being developed as a potential agent for the treatment of severe and complicated malaria. A risk assessment of the therapeutic index and related hematological changes of AS and artelinate (AL) following daily intravenous injection for 3 days was conducted in Plasmodium berghei-infected and uninfected rats. The minimum doses of AS and AL for parasitemia suppression were 2.3 and 2.5 mg/kg, respectively, and the suppressive doses for half parasitemia (SD50) were 7.4 and 8.6 mg/kg, respectively. The maximum tolerated dose (MTD) for AS was 240 mg/kg with a therapeutic index of 32.6. The MTD for AL was 80 mg/kg with a therapeutic index of 9.3. Hematological changes were studied on days 1 and 8 after the final dosing. In both AS- and AL-treated rats, dose-dependent and rapidly reversible hematological changes (significant reductions in RBC, HCT, Hb, and reticulocyte levels) were seen in the peripheral blood. Bone marrow evaluation revealed a statistically significant reduction in the myeloid/erythroid ratio only at the highest dose of AS (240 mg/kg), albeit still within the normal ratio range (1.0-1.51.0). Looking at the respective therapeutic indices the authors have concluded that AS is much safer than AL. Both drugs induced hematological changes in rats that parallel the dose-dependent, reversible anemia and reticulocytopenia previously reported in animals and humans. However, no significant bone marrow depression was seen for either agent.
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Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Plasmodium berghei
/
Sesquiterpenos
/
Artemisininas
/
Malaria
/
Antimaláricos
Tipo de estudio:
Etiology_studies
/
Prognostic_studies
/
Risk_factors_studies
Límite:
Animals
Idioma:
En
Revista:
Int J Toxicol
Asunto de la revista:
TOXICOLOGIA
Año:
2005
Tipo del documento:
Article
País de afiliación:
Estados Unidos