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.
Footnotes
-
Send reprint requests to: Dr. Michael Ashton, Division of Biopharmaceutics & Pharmacokinetics, Uppsala University Biomedical Center, Box 580, 751 23 Uppsala, Sweden.
-
Supported by Grant SWE-93-165 from the Swedish Agency for Research Cooperation with Developing Countries (SAREC). Partly presented at the 1st European Conference of Tropical Medicine, Hamburg, 1995 (Abstract H128).
- Abbreviations used are::
- CL/F
- oral clearance values
- AUC
- areas under the plasma concentration-time curve
- Received April 30, 1997.
- Accepted October 14, 1997.
- The American Society for Pharmacology and Experimental Therapeutics
DMD articles become freely available 12 months after publication, and remain freely available for 5 years.Non-open access articles that fall outside this five year window are available only to institutional subscribers and current ASPET members, or through the article purchase feature at the bottom of the page.
|