Publication: Oral artesunate dose-response relationship in acute falciparum malaria
Issued Date
2002-02-28
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ISSN
00664804
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2-s2.0-0036168512
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Mahidol University
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SCOPUS
Bibliographic Citation
Antimicrobial Agents and Chemotherapy. Vol.46, No.3 (2002), 778-782
Suggested Citation
Brian J. Angus, Itaporn Thaiaporn, Kenechanh Chanthapadith, Yupin Suputtamongkol, Nicholas J. White Oral artesunate dose-response relationship in acute falciparum malaria. Antimicrobial Agents and Chemotherapy. Vol.46, No.3 (2002), 778-782. doi:10.1128/AAC.46.3.778-782.2002 Retrieved from: https://repository.li.mahidol.ac.th/handle/123456789/20531
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Title
Oral artesunate dose-response relationship in acute falciparum malaria
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Abstract
The combination of an oral artemisinin derivative (usually artesunate) and mefloquine has become standard treatment for multidrug-resistant falciparum malaria in several parts of Southeast Asia. The doses of artesunate used in monotherapy and combination treatment have largely been derived empirically. In order to characterize the in vivo dose-response relationship for artesunate and thus rationalize dosing, 47 adult patients with acute uncomplicated falciparum malaria and parasitemia ≥1% were randomized to receive a single oral dose of artesunate varying between 0 and 250 mg together with a curative dose of oral mefloquine. Acceleration of parasite clearance was used as the pharmacodynamic variable. An inhibitory sigmoidal maximum effect (Emax) pharmacodynamic model typical of a dose-response curve was fitted to the relationship between dose and shortening of parasite clearance time (PCT). The Emaxwas estimated as 28.6 h, and the 50% effective concentration was 1.6 mg/kg of body weight. These results imply that there is no reduction in PCTs with the use of single oral doses of artesunate higher than 2 mg/kg, and this therefore reflects the average lower limit of the maximally effective dose.