Retrospective analysis of artemisinin pharmacokinetics: application of a semiphysiological autoinduction model.

• AIMS: 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.

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper -- Farmaceutiska vetenskaper (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Basic Medicine -- Pharmaceutical Sciences (hsv//eng)

Nyckelord

Adult

Antimalarials

pharmacokinetics

therapeutic use

Artemisinins

pharmacokinetics

therapeutic use

Dose-Response Relationship

Drug

Drug Administration Schedule

Humans

Malaria

drug therapy

Male

Middle Aged

Models

Biological

Retrospective Studies

Publikations- och innehållstyp

ref (ämneskategori)

art (ämneskategori)