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Efficacy comparison of intravenous artelinate and artesunate in Plasmodium berghei-infected Sprague-Dawley rats

Published online by Cambridge University Press:  30 April 2003

Q. G. LI ,
Y. Z. SI ,
P. LEE ,
E. WONG ,
L. H. XIE ,
D. E. KYLE  and
G. S. DOW
Q. G. LI
Affiliation:
Department of Pharmacology, Division of Experimental Therapeutics, Walter Reed Army Institute of Research, 503 Robert Grant Avenue, Silver Spring, MD 20910, USA
Y. Z. SI
Affiliation:
Department of Pharmacology, Division of Experimental Therapeutics, Walter Reed Army Institute of Research, 503 Robert Grant Avenue, Silver Spring, MD 20910, USA
P. LEE
Affiliation:
Department of Pharmacology, Division of Experimental Therapeutics, Walter Reed Army Institute of Research, 503 Robert Grant Avenue, Silver Spring, MD 20910, USA
E. WONG
Affiliation:
Department of Pharmacology, Division of Experimental Therapeutics, Walter Reed Army Institute of Research, 503 Robert Grant Avenue, Silver Spring, MD 20910, USA
L. H. XIE
Affiliation:
Department of Pharmacology, Division of Experimental Therapeutics, Walter Reed Army Institute of Research, 503 Robert Grant Avenue, Silver Spring, MD 20910, USA
D. E. KYLE
Affiliation:
Department of Pharmacology, Division of Experimental Therapeutics, Walter Reed Army Institute of Research, 503 Robert Grant Avenue, Silver Spring, MD 20910, USA
G. S. DOW
Affiliation:
Department of Pharmacology, Division of Experimental Therapeutics, Walter Reed Army Institute of Research, 503 Robert Grant Avenue, Silver Spring, MD 20910, USA
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Abstract

This paper reports the comparative antimalarial efficacy of intravenous artelinate and artesunate in rats. Prior to efficacy experiments, a Plasmodium berghei–Sprague-Dawley rat model of malaria was developed, in which the clearance effects of intravenous drugs could be readily compared. In efficacy experiments, groups of P. berghei-infected rats were given 3 daily intravenous treatments of artelinate or artesunate at molar equivalent dose rates (total of 0–191·2 μmoles/kg). Artelinate was superior to artesunate in terms of clearance (100% clearance dose of 95·6 μmoles/kg (40 mg/kg) versus 191·2 μmoles/kg for AS (73·4 mg/kg)) and parasite clearance time (1·7±0·5 days for AL versus 2·7±0·5 days for AS at a dose rate of 191·2 μmoles/kg, P<0·01). No frank clinical toxicity was observed, though both artesunate and artelinate induced dose-related vascular necrosis at the site of injection. The necrosis was less severe and reversible when the drugs were administered via femoral, rather than tail/foot veins. The data suggest that the P. berghei–7-week-old Sprague-Dawley rat model of malaria is reproducible and useful for assessing the efficacy of antimalarials and that artelinate is at least as potent, and safe, as artesunate, the leading clinical treatment for severe malaria.

Keywords

artesunateartelinateantimalarialsPlasmodium bergheirat malaria model
Type
Research Article
Information
Parasitology , Volume 126 , Issue 4 , April 2003 , pp. 283 - 291
Copyright
© 2003 Cambridge University Press

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