TY - JOUR T1 - Artemisinin Pharmacokinetics is Time-Dependent during Repeated Oral Administration in Healthy Male Adults JF - Drug Metabolism and Disposition JO - Drug Metab Dispos SP - 25 LP - 27 VL - 26 IS - 1 AU - Michael Ashton AU - Trinh Ngoc Hai AU - Nguyen Duy Sy AU - Dinh Xuan Huong AU - Nguyen Van Huong AU - Nguyen Thi Niêu AU - Le Dinh Công Y1 - 1998/01/01 UR - http://dmd.aspetjournals.org/content/26/1/25.abstract N2 - 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 ER -