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The Pharmacokinetics of a Single Dose of Artemisinin in Patients with Uncomplicated Falciparum Malaria

The pharmacokinetics of artemisinin was studied in 11 Vietnamese patients with uncomplicated falciparum malaria after a single 500 mg oral dose. Curative treatment with mefloquine (15 mg/kg) was provided 24 hr after the artemisinin dose. Artemisinin concentrations were measured by high-performance liquid chromatography with electrochemical detection. The following pharmacokinetic results were found (all mean ± SD): calculated volume of distribution/bioavailability = 22.8 ± 16.6 L.kg^-1, mean absorption time = 1.16 ± 0.92 hr, calculated maximum concentration = 364 ± 250 µg.L^-1 occurring at 2.88 ± 1.71 hr after drug intake, and an elimination half-life of 2.72 ± 1.76 hr. Bioavailability was low. These results do not differ from results in healthy subjects. Parasites disappeared rapidly, with a mean parasite clearance time of 36 hr. No relationship was found between pharmacokinetics and the parasite elimination rate. Tolerance to the single dose of artemisinin was good. No adverse effects were detected. In conclusion, pharmacokinetics of a single dose of artemisinin for uncomplicated falciparum malaria is not different from findings in healthy subjects. A single dose of 500 mg of artemisinin is effective in reducing parasitemia in nonsevere falciparum malaria and is well-tolerated.

^* In collaboration with the following members of the Bach Mai-Amsterdam Research Group on Artemisinin: Bob van de Berg (Amsterdam, Department of Clinical Pharmacology and Pharmacotherapy), Jan Butter (Amsterdam, Department of Clinical Pharmacology and Pharmacotherapy), Bui Hien (Hanoi, Institute for Clinical Research in Tropical Medicine), Richard P. Koopmans (Amsterdam, Department of Clinical Pharmacology and Pharmacotherapy), Els Portier (Amsterdam, Department of Clinical Pharmacology and Pharmacotherapy), Pham Song (Hanoi, Institute for Clinical Research in Tropical Medicine), and Dang Cam Thach (Hanoi, Institute of Malariology, Parasitology, and Entomology).