Sara Asimus1, Toufigh Gordi. 1. Sahlgrenska Academy at Göteborg University, Department of Pharmacology, Göteborg, Sweden.
Abstract
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.
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 malariapatients 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.
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