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The importance of clinical pharmacokinetic–pharmacodynamic studies in unraveling the determinants of early and late tuberculosis outcomes

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ipk_2017_0004_Sloan.pdf (1.267Mb)
Date
07/2017
Author
McCallum, Andrew D
Sloan, Derek James
Keywords
Clinical trials
Compartmental pharmacokinetics
Multidrug-resistant tuberculosis
Pharmacogenetics
Pharmacokinetics-pharmacodynamics
Therapeutic drug monitoring
Tuberculosis
RM Therapeutics. Pharmacology
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Abstract
Tuberculosis remains a major infectious cause of morbidity and mortality worldwide. Current antibiotic regimens, constructed prior to the development of modern pharmacokinetic-pharmacodynamic (PK–PD) tools, are based on incomplete understanding of exposure–response relationships in drug susceptible and multidrug resistant tuberculosis. Preclinical and population PK data suggest that clinical PK–PD studies may enable therapeutic drug monitoring for some agents and revised dosingf or others. Future clinical PK–PD challenges include: incorporation of PK methods to assay free concentrations for all active metabolites; selection of appropriate early outcome measures which reflect therapeutic response; elucidation of genetic contributors to interindividual PK variability; conduct of targeted studies on special populations (including children); and measurement of PK–PD parameters at the site of disease.
Citation
McCallum , A D & Sloan , D J 2017 , ' The importance of clinical pharmacokinetic–pharmacodynamic studies in unraveling the determinants of early and late tuberculosis outcomes ' , International Journal of Pharmacokinetics , vol. 2 , no. 3 , pp. 195-212 . https://doi.org/10.4155/ipk-2017-0004
Publication
International Journal of Pharmacokinetics
Status
Peer reviewed
DOI
https://doi.org/10.4155/ipk-2017-0004
ISSN
2053-0846
Type
Journal item
Rights
Copyright the Author(s) 2017. This work is licensed under the Attribution-NonCommercial-NoDerivatives 4.0 Unported License. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-nd/4.0/
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  • University of St Andrews Research
URI
http://hdl.handle.net/10023/12035

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