Pharmacokinetics of oral artesunate in children with moderately severe Plasmodium falciparum malaria.
The pharmacokinetic properties of oral artesunate (3 mg/kg) were determined in 10 Vietnamese children, aged from 6 to 15 years, with acute falciparum malaria of moderate severity. Plasma concentrations were measured using a bioassay and expressed in terms of antimalarial activity equivalent to dihydroartemisinin, the principal biologically active metabolite. Oral artesunate was absorbed rapidly with a mean time to peak plasma bioactivity of 1.7 h (95% confidence interval [95% CI] 0.8-2.6). There was wide variation in peak plasma concentrations with a mean value equivalent to 664 ng of dihydroartemisinin/mL (95% CI 387-9410, range 179-1395) and a four-fold variation in the area under the plasma concentration-time curves. Elimination from plasma was rapid with a mean (95% CI) half-life of 1.0 h (95% CI 0.8-1.4). Plasma antimalarial levels were below the limit of detection in all cases by 12 h, despite the relatively high dose of artesunate used. Oral artesunate is rapidly absorbed and rapidly eliminated in children with moderately severe malaria but there is considerable variation between individuals.
Bethell
D B
DB
Wellcome Trust Clinical Research Unit, Centre for Tropical Diseases, Cho Quan Hospital, Ho Chi Minh City, Viet Nam.
Teja-Isavadharm
P
P
Cao
X T
XT
Pham
T T
TT
Ta
T T
TT
Tran
T N
TN
Nguyen
T T
TT
Pham
T P
TP
Kyle
D
D
Day
N P
NP
White
N J
NJ
D000284:Administration, Oral; D000293:Adolescent; D000962:Antimalarials / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use; D037621:Artemisinins; D000077332:Artesunate; D001681:Biological Assay; D002648:Child; D005260:Female; D006801:Humans; D016778:Malaria, Falciparum / Q000188:drug therapy / Q000378:metabolism*; D008297:Male; D012717:Sesquiterpenes / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use
D000962:Antimalarials; D037621:Artemisinins; D012717:Sesquiterpenes; D000077332:Artesunate