RT Journal Article
SR Electronic
T1 Artemisinin Pharmacokinetics is Time-Dependent during Repeated Oral Administration in Healthy Male Adults
JF Drug Metabolism and Disposition
JO Drug Metab Dispos
FD American Society for Pharmacology and Experimental Therapeutics
SP 25
OP 27
VO 26
IS 1
A1 Michael Ashton
A1 Trinh Ngoc Hai
A1 Nguyen Duy Sy
A1 Dinh Xuan Huong
A1 Nguyen Van Huong
A1 Nguyen Thi Niêu
A1 Le Dinh Công
YR 1998
UL http://dmd.aspetjournals.org/content/26/1/25.abstract
AB 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. The American Society for Pharmacology and Experimental Therapeutics