Phamacokinetics of a single oral dose of dihydroartemisinin in Vietnamese healthy volunteers.
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: t(lag) 0.41 (0.09-0.78) hours, t(1/2z) 0.58 (0.17-1.43) hours, t(max) 1.6 (1.1-2.2) hours, Cmax 466 (128-787) ng/ml. Cmax/dosage 97.7 (27.2-124.6) ng/ml, t(1/2z) 2.0 (1.5-3.4) hours, AUC 1867 (420-3535) ng x h/ml, AUC/dosage 364.3 (89.3-559.7) ng x 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 t(max) of DHA formulation was comparable with that of DHA metabolite of artemisinin derivatives. The t(1/2z) was 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.
Le
N H
NH
Clinical Pharmacology Unit, Faculty of Tropical Medicine, Mahidol University, Phyathai, Bangkok, Thailand.
Na-Bangchang
K
K
Le
T D
TD
Thrinh
K A
KA
Karbwang
J
J
D000284:Administration, Oral; D000328:Adult; D000962:Antimalarials / Q000008:administration & dosage* / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics*; D037621:Artemisinins; D002626:Chemistry, Pharmaceutical; D002851:Chromatography, High Pressure Liquid; D016903:Drug Monitoring / Q000379:methods; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D008297:Male; D012717:Sesquiterpenes / Q000008:administration & dosage* / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics*; D013997:Time Factors; D014744:Vietnam
D000962:Antimalarials; D037621:Artemisinins; D012717:Sesquiterpenes; C039060:artenimol