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|Title:||Phamacokinetics of a single oral dose of dihydroartemisinin in Vietnamese healthy volunteers|
|Authors:||Le Ngoc Hung|
Le Thi Diem Thuy
Thrinh Kim Anh
Cho Ray Hospital
|Citation:||Southeast Asian Journal of Tropical Medicine and Public Health. Vol.30, No.1 (1999), 11-16|
|Abstract:||Pharmacokinetics of a 240 mg single dose of oral dihydroartemisinin (DHA) was investigated in 8 healthy (5 males, 3 females) Vietnamese volunteers. Plasma concentrations were measured by high-performance liquid chromatography with electrochemical detection in the reductive mode. The concentration time profile of DHA was fitted with one-compartment model with a lag time. Pharmacokinetics of DHA is comparable between males and females even when adjusted with dosage. The median (range) values of pooled pharmacokinetics of oral DHA were: tlag0.41 (0.09-0.78) hours, t1/2a0.58 (0.17-1.43) hours, tmax1.6 (1.1-2.2) hours, Cmax466 (128-787) ng/ml. Cmax/dosage 97.7 (27.2-124.6) ng/ml, t1/2z2.0 (1.5-3.4) hours, AUC 1867 (420-3535) ng.h/ml, AUC/dosage 364.3 (89.3-559.7) ng.h/ml/dosage, Cl/f 45.8 (30.0-190.0) ml/min/kg, Vz/f 8.0 (5.5-29.9) l/kg. Interindividual variation was large, the coefficients of variation (CV) were 47.8% and 45.3% respectively to AUC and Cmax. The tmaxof DHA formulation was comparable with that of DHA metabolite of artemisinin derivatives. The t1/2zwas longer and shorter than that of DHA metabolites of oral formulations of artesunate and artemether, respectively. For monotherapeutic regimen(s) of DHA, dosing frequency of at least twice a day is suggested. Combined regimen(s) of DHA with other potent, long half-life antimalarials may also be an alternative approach.|
|Appears in Collections:||Scopus 1991-2000|
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