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Reprint of “Pharmacokinetic modelling of the anti-malarial drug artesunate and its active metabolite dihydroartemisinin” |
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| Authors: | Adam J. Hall Michael J. Chappell John A.D. Aston Stephen A. Ward |
| Affiliation: | 1. Departments of Mathematics and Statistics, University of Warwick, Gibbet Hill Road, Coventry CV4 7AL, UK;2. School of Engineering, University of Warwick, Gibbet Hill Road, Coventry CV4 7AL, UK;3. Department of Statistics, University of Warwick, Gibbet Hill Road, Coventry CV4 7AL, UK;4. Liverpool School of Tropical Medicine, Pembroke Place, Liverpool L3 5QA, UK |
| Abstract: | A four compartment mechanistic mathematical model is developed for the pharmacokinetics of the commonly used anti-malarial drug artesunate and its principle metabolite dihydroartemisinin following oral administration of artesunate. The model is structurally unidentifiable unless additional constraints are imposed. Combinations of mechanistically derived constraints are considered to assess their effects on structural identifiability and on model fits. Certain combinations of the constraints give rise to locally or globally identifiable model structures. |
| Keywords: | Mathematical models Biomedical systems Drug kinetics Structural identifiability Parameter estimation Sensitivity analysis |
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