Artemisinin pharmacokinetics is time-dependent during repeated oral administration in healthy male adults.
The pharmacokinetics of the antimalarial artemisinin exhibited an unusual time dependency during a 7-day oral daily regimen of 500 mg in 10 healthy, male Vietnamese adults. Artemisinin areas under the plasma concentration-time curve (AUC) decreased to 34% (median) by day 4 with a further decrease by day 7 to only 24% of values obtained after the first day of administration. In seven subjects restudied after a 2-week washout period, artemisinin AUCs had almost normalized, demonstrating the reversibility of the time-dependent drug disposition. The results suggest artemisinin exhibits an auto-inductive effect on drug metabolism of an unusual magnitude. This may partly explain why some patients on standard doses, due to subparasiticidal drug levels toward the end of a standard regimen, do not completely clear parasites. Further, the possibility of drug-drug metabolic interactions during combination regimens is implicated.
Ashton
M
M
Division of Biopharmaceutics & Pharmacokinetics, Department of Pharmacy, Uppsala University, Uppsala, Sweden.
Hai
T N
TN
Sy
N D
ND
Huong
D X
DX
Van Huong
N
N
Niêu
N T
NT
Công
L D
LD
D000284:Administration, Oral; D000328:Adult; D000962:Antimalarials / Q000008:administration & dosage / Q000493:pharmacokinetics*; D037621:Artemisinins; D006801:Humans; D007958:Leukocyte Count / Q000187:drug effects; D008297:Male; D012717:Sesquiterpenes / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D013997:Time Factors
D000962:Antimalarials; D037621:Artemisinins; D012717:Sesquiterpenes; C031327:artemisinin