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Antimicrobial Agents and Chemotherapy, April 2000, p. 972-977, Vol. 44, No. 4
Faculty of Tropical Medicine, Mahidol
University,1 Department of Medicine,
Siriraj Hospital,3 and Department of
Immunology and Medicine, Armed Forces Research Institute of Medical
Sciences,4 Bangkok, Thailand; Centre for
Tropical Medicine, Nuffield Department of Clinical Medicine, John
Radcliffe Hospital, Headington, Oxford,2
and Liverpool School of Tropical Medicine,
Liverpool,6 United Kingdom; and National
Centre for Drug Research, Universiti Sains Malaysia, Penang,
Malaysia5
Received 8 March 1999/Returned for modification 25 August
1999/Accepted 8 January 2000
The pharmacokinetic properties of oral and intravenous artesunate
(2 mg/kg of body weight) were studied in 19 adult patients with acute
uncomplicated Plasmodium falciparum malaria by using a
randomized crossover design. A sensitive bioassay was used to measure
the antimalarial activity in plasma which results from artesunate and
its principal metabolite, dihydroartemisinin. The oral study was
repeated with 15 patients during convalescence. The mean absolute oral
bioavailability of the antimalarial agent in patients with acute
malaria was 61% (95% confidence interval [CI], 52 to 70%). The
absorption and elimination of oral artesunate were rapid, with a mean
elimination half-life of antimalarial activity of 43 min (95% CI, 33 to 53 min). Following oral administration to patients with acute
falciparum malaria, peak antimalarial activity in plasma and the area
under the plasma concentration-time curve were approximately double
those during convalescence and the apparent volume of distribution and
clearance were approximately half those during convalescence
(P
0066-4804/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.
Antimalarial Bioavailability and Disposition of
Artesunate in Acute Falciparum Malaria
0.005). Acute malaria is associated with a
significant reduction in the clearance of artesunate-associated antimalarial activity.
*
Corresponding author. Mailing address: Faculty of
Tropical Medicine, Mahidol University, 420/6 Rajvithi Rd., Bangkok
10400, Thailand. Phone: (66) 2 246 0832. Fax: (66) 2 246 7795. E-mail: fnnjw{at}diamond.mahidol.ac.th.
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