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

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.