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Antimicrobial Agents and Chemotherapy, December 2002, p. 3933-3939, Vol. 46, No. 12
0066-4804/02/$04.00+0     DOI: 10.1128/AAC.46.12.3933-3939.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

Intramuscular Bioavailability and Clinical Efficacy of Artesunate in Gabonese Children with Severe Malaria

Department of Infectious Diseases, St. George's Hospital Medical School, London SW17 ORE, United Kingdom,¹ Department of Parasitology, Mycology and Tropical Medicine, Faculty of Medicine, University of Libreville, Libreville,² Medical Research Unit, Albert Schweitzer Hospital, Lambaréné, Gabon,⁴ Department of Parasitology, Eberhard Karls Universität, Tübingen, Germany,³ Parasitology Department, Institut de Médecine Tropicale du Service de Santé des Armées, 13998, Marseille Armées, France⁵

Received 10 April 2002/ Returned for modification 12 August 2002/ Accepted 3 September 2002

Artesunate (ARS) is a water-soluble artemisinin derivative that is a potential alternative to quinine for the treatment of severe childhood malaria. We studied the pharmacokinetics and bioavailability of ARS given by the intramuscular (i.m.) route in an open crossover study design. Fourteen children were randomized to receive intravenous (i.v.) ARS in a loading dose (2.4 mg/kg of body weight) followed 12 h later by an i.m. dose (1.2 mg/kg) (group I), and 14 children were randomized to receive i.m. ARS (2.4 mg/kg) followed by an i.v. dose of ARS (1.2 mg/kg) (group II). We carried out a two-compartment analysis of ARS and dihydroartemisinin (DHA; the principal antimalarial metabolite) levels in 21 children (groups I and II combined). Absorption of i.m. ARS was rapid, with the maximum concentration of DHA in serum being achieved in less than 1 h in most children (median time to the maximum concentration of drug in serum, 35.1 min; range, 10.8 to 71.9 min). The absolute bioavailability of DHA was a median of 86.4% (range, 11.4 to 462.1%), the median steady-state volume of distribution was 1.3 liters/kg (range, 0.5 to 7.9 liters/kg), and the median clearance was 0.028 liters/kg/min (range, 0.001 to 1.58 liters/kg/min). There were no major adverse events attributable to ARS. Parasite clearance kinetics were comparable between the two treatment groups. These results support the use of i.m. ARS in children with severe malaria.

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