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Retrospective analysis of artemisinin pharmacokinetics: application of a semiphysiological autoinduction model
Author(s) -
Asimus Sara,
Gordi Toufigh
Publication year - 2007
Publication title -
british journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.216
H-Index - 146
eISSN - 1365-2125
pISSN - 0306-5251
DOI - 10.1111/j.1365-2125.2006.02844.x
Subject(s) - artemisinin , pharmacokinetics , pharmacology , nonmem , drug , chemistry , medicine , plasmodium falciparum , malaria , immunology
What is already known about this subject? • A previous semiphysiological model has been published, describing the time course of the autoinduction of artemisinin. • The model, which was based on saliva sampling, has been successfully applied in another set of saliva data. What this study adds? • In this report, we applied the same model to plasma data from six clinical studies involving healthy volunteers and malaria patients. • The model performed well and we suggest that it could be used as a general model in cases of time‐dependent pharmacokinetics and drug‐drug interactions. Aims To describe the time‐course of the autoinduction of artemisinin by applying a semiphysiological 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 semiphysiological 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.