Source:http://linkedlifedata.com/resource/pubmed/id/16126619
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
4
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| pubmed:dateCreated |
2005-8-29
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| pubmed:abstractText |
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 (1.0-1.5:1.0). 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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| pubmed:language |
eng
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| pubmed:journal | |
| pubmed:citationSubset |
IM
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| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Antimalarials,
http://linkedlifedata.com/resource/pubmed/chemical/Artemisinins,
http://linkedlifedata.com/resource/pubmed/chemical/Sesquiterpenes,
http://linkedlifedata.com/resource/pubmed/chemical/artelinic acid,
http://linkedlifedata.com/resource/pubmed/chemical/artesunate
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| pubmed:status |
MEDLINE
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| pubmed:issn |
1091-5818
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| pubmed:author | |
| pubmed:issnType |
Print
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| pubmed:volume |
24
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| pubmed:owner |
NLM
|
| pubmed:authorsComplete |
Y
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| pubmed:pagination |
251-64
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| pubmed:dateRevised |
2006-11-15
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| pubmed:meshHeading |
pubmed-meshheading:16126619-Anemia,
pubmed-meshheading:16126619-Animals,
pubmed-meshheading:16126619-Antimalarials,
pubmed-meshheading:16126619-Artemisinins,
pubmed-meshheading:16126619-Body Weight,
pubmed-meshheading:16126619-Dose-Response Relationship, Drug,
pubmed-meshheading:16126619-Erythrocyte Count,
pubmed-meshheading:16126619-Female,
pubmed-meshheading:16126619-Hematocrit,
pubmed-meshheading:16126619-Malaria,
pubmed-meshheading:16126619-Male,
pubmed-meshheading:16126619-Maximum Tolerated Dose,
pubmed-meshheading:16126619-Parasitemia,
pubmed-meshheading:16126619-Plasmodium berghei,
pubmed-meshheading:16126619-Rats,
pubmed-meshheading:16126619-Rats, Sprague-Dawley,
pubmed-meshheading:16126619-Reticulocyte Count,
pubmed-meshheading:16126619-Risk Assessment,
pubmed-meshheading:16126619-Sesquiterpenes,
pubmed-meshheading:16126619-Sex Factors,
pubmed-meshheading:16126619-Therapeutic Equivalency,
pubmed-meshheading:16126619-Time Factors
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| pubmed:articleTitle |
Risk assessment and therapeutic indices of artesunate and artelinate in Plasmodium berghei-infected and uninfected rats.
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| pubmed:affiliation |
Division of Experimental Therapeutics, Walter Reed Army Institute of Research, Silver Spring, Maryland 20307-5100, USA.
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| pubmed:publicationType |
Journal Article,
Comparative Study,
Research Support, U.S. Gov't, Non-P.H.S.
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