Retrospective analysis of artemisinin pharmacokinetics: application of a semiphysiological autoinduction model.
OBJECTIVE
To describe the time-course of the autoinduction of artemisinin by applying a semi-physiological pharmacokinetic model.


METHODS
Plasma concentration-time data from six clinical studies involving oral administration of artemisinin to healthy subjects and malaria patients were included in the analysis. NONMEM was used to apply a semi-physiological model incorporating metabolizing enzymes and a pharmacokinetic model including a separate hepatic compartment.


RESULTS
The model described the data well. The hepatic extraction ratio increased from 0.74 at pre-induced conditions to 0.98 after autoinduction of metabolism.


CONCLUSIONS
Our model successfully described the time-course of autoinduction of metabolism of artemisinin in subjects receiving oral artemisinin.
Asimus
Sara
S
Sahlgrenska Academy at Göteborg University, Department of Pharmacology, Göteborg, Sweden.
Gordi
Toufigh
T
D000328:Adult; D000962:Antimalarials / Q000493:pharmacokinetics* / Q000627:therapeutic use; D037621:Artemisinins / Q000493:pharmacokinetics* / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D006801:Humans; D008288:Malaria / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D008954:Models, Biological; D012189:Retrospective Studies
D000962:Antimalarials; D037621:Artemisinins