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Drug Metab Dispos ; 26(1): 25-7, 1998 Jan.
Article in English | MEDLINE | ID: mdl-9443848

ABSTRACT

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.


Subject(s)
Antimalarials/pharmacokinetics , Artemisinins , Sesquiterpenes/pharmacokinetics , Administration, Oral , Adult , Antimalarials/administration & dosage , Humans , Leukocyte Count/drug effects , Male , Sesquiterpenes/administration & dosage , Sesquiterpenes/blood , Time Factors
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