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Pharmacokinetic modelling of the anti-malarial drug artesunate and its active metabolite dihydroartemisinin
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Hall, Adam J., Chappell, M. J. (Michael J.), Aston, John A. D. and Ward, Stephen A. (2013) Pharmacokinetic modelling of the anti-malarial drug artesunate and its active metabolite dihydroartemisinin. Computer Methods and Programs in Biomedicine . doi:10.1016/j.cmpb.2013.05.010 ISSN 0169-2607.
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Official URL: http://dx.doi.org/10.1016/j.cmpb.2013.05.010
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.
Initial validation of the model under various combinations of the constraints leading to identifiable model structures was performed against a dataset of artesunate and dihydroartemisinin concentration–time profiles of 19 malaria patients. When all the discussed constraints were imposed on the model, the resulting globally identifiable model structure was found to fit reasonably well to those patients with normal drug absorption profiles. However, there is wide variability in the fitted parameters and further investigation is warranted.
Item Type: | Journal Article | ||||
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Subjects: | R Medicine > RA Public aspects of medicine > RA0421 Public health. Hygiene. Preventive Medicine R Medicine > RM Therapeutics. Pharmacology R Medicine > RS Pharmacy and materia medica |
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Divisions: | Faculty of Science, Engineering and Medicine > Engineering > Engineering Faculty of Science, Engineering and Medicine > Science > Mathematics Faculty of Science, Engineering and Medicine > Science > Statistics |
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Library of Congress Subject Headings (LCSH): | Antimalarials, Artemisinin, Malariotherapy, Drugs -- Testing, Pharmacokinetics | ||||
Journal or Publication Title: | Computer Methods and Programs in Biomedicine | ||||
Publisher: | Elsevier Ireland Ltd. | ||||
ISSN: | 0169-2607 | ||||
Official Date: | 18 July 2013 | ||||
Dates: |
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DOI: | 10.1016/j.cmpb.2013.05.010 | ||||
Status: | Peer Reviewed | ||||
Publication Status: | Published | ||||
Access rights to Published version: | Open Access (Creative Commons) | ||||
Date of first compliant deposit: | 25 December 2015 | ||||
Date of first compliant Open Access: | 25 December 2015 | ||||
Funder: | Engineering and Physical Sciences Research Council (EPSRC) | ||||
Grant number: | EP/H023364/1 | ||||
Adapted As: | Adam J. Hall, Michael J. Chappell, John A.D. Aston, Stephen A. Ward. (2014). Reprint of “Pharmacokinetic modelling of the anti-malarial drug artesunate and its active metabolite dihydroartemisinin”. http://dx.doi.org/10.1016/j.cmpb.2013.12.001 |
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