Absence of time-dependent artesunate pharmacokinetics in healthy subjects during 5-day oral administration.
OBJECTIVE
The aim of the present study was to investigate the existence of time-dependent pharmacokinetics of artesunate (ARS) during 5 consecutive days of oral administration to 10 healthy Vietnamese subjects (aged 21-52 years and weighing 49-90 kg).


METHODS
Each volunteer received 200 mg oral doses of ARS once daily for 5 consecutive days. Blood samples (3 ml each) were collected on days 1 and 5 at 0 (before dosing), 0.5, 1, 2, 3, 4, and 6 h after drug administration. During days 2, 3, and 4, the same volumes of blood were collected at 0, 1, 2, and 4 h after dosing. Plasma ARS and dihydroartemisinin (DHA) were measured using high-performance liquid chromatography-mass spectrometry (LC-MS).


RESULTS
Results did not show evidence of time-dependency for ARS or the active plasma metabolite DHA. There were no differences in the concentrations of ARS and DHA at all sampling times on days 1 and 5. In addition, the pharmacokinetics of both compounds were similar on days 1 and 5. This finding confirms that the enzyme auto-induction in drug metabolism may not be characteristic of the endoperoxide sesquiterpene antimalarial group.
Diem Thuy
L T
LT
Faculty of Allied Health Sciences, Pharmacology and Toxicology Unit, Graduate Program in Biomedical Sciences, Thammasat University, Rangsit Campus, Pathumthani, Thailand.
Ngoc Hung
L
L
Danh
P T
PT
Na-Bangchang
K
K
D000284:Administration, Oral; D000328:Adult; D000962:Antimalarials / Q000008:administration & dosage / Q000097:blood / Q000378:metabolism / Q000493:pharmacokinetics*; D019540:Area Under Curve; D037621:Artemisinins / Q000008:administration & dosage / Q000097:blood / Q000378:metabolism / Q000493:pharmacokinetics*; D000077332:Artesunate; D004334:Drug Administration Schedule; D006207:Half-Life; D006801:Humans; D008297:Male; D008657:Metabolic Clearance Rate; D008875:Middle Aged; D013995:Time; D014744:Vietnam; D055815:Young Adult
D000962:Antimalarials; D037621:Artemisinins; D000077332:Artesunate; C039060:artenimol