Publication: World Antimalarial Resistance Network (WARN) IV: clinical pharmacology
1
Accepted Date
2007-09-06
Issued Date
2007-09-06
Copyright Date
2007
Resource Type
Language
eng
ISSN
1475-2875 (electronic)
Rights
Mahidol University
Rights Holder(s)
BioMed Central
Bibliographic Citation
Barnes KI, Lindegardh N, Ogundahunsi O, Olliaro P, Plowe CV, Randrianarivelojosia M, et al. World Antimalarial Resistance Network (WARN) IV: clinical pharmacology. Malar J. 2007 Sep 6;6:122.
Suggested Citation
Barnes, Karen I., Lindegardh, Niklas, Ogundahunsi, Olumide, Olliaro, Piero, Plowe, Christopher V., Randrianarivelojosia, Milijaona, Gbotosho, Grace O, Watkins, William M., Sibley, Carol H., White, Nicholas J. World Antimalarial Resistance Network (WARN) IV: clinical pharmacology. Barnes KI, Lindegardh N, Ogundahunsi O, Olliaro P, Plowe CV, Randrianarivelojosia M, et al. World Antimalarial Resistance Network (WARN) IV: clinical pharmacology. Malar J. 2007 Sep 6;6:122.. doi:10.1186/1475-2875-6-122 Retrieved from: https://repository.li.mahidol.ac.th/handle/123456789/707
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Title
World Antimalarial Resistance Network (WARN) IV: clinical pharmacology
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Abstract
A World Antimalarial Resistance Network (WARN) database has the potential to
improve the treatment of malaria, through informing current drug selection and
use and providing a prompt warning of when treatment policies need changing. This
manuscript outlines the contribution and structure of the clinical pharmacology
component of this database. The determinants of treatment response are
multi-factorial, but clearly providing adequate blood concentrations is pivotal
to curing malaria. The ability of available antimalarial pharmacokinetic data to
inform optimal dosing is constrained by the small number of patients studied,
with even fewer (if any) studies conducted in the most vulnerable populations.
There are even less data relating blood concentration data to the therapeutic
response (pharmacodynamics). By pooling all available pharmacokinetic data, while
paying careful attention to the analytical methodologies used, the limitations of
small (and thus underpowered) individual studies may be overcome and factors that
contribute to inter-individual variability in pharmacokinetic parameters defined.
Key variables for pharmacokinetic studies are defined in terms of patient (or
study subject) characteristics, the formulation and route of administration of
the antimalarial studied, the sampling and assay methodology, and the approach
taken to data analysis. Better defining these information needs and criteria of
acceptability of pharmacokinetic-pharmacodynamic (PK-PD) studies should
contribute to improving the quantity, relevance and quality of these studies. A
better understanding of the pharmacokinetic properties of antimalarials and a
more clear definition of what constitutes "therapeutic drug levels" would allow
more precise use of the term "antimalarial resistance", as it would indicate when
treatment failure is not caused by intrinsic parasite resistance but is instead
the result of inadequate drug levels. The clinical pharmacology component of the
WARN database can play a pivotal role in monitoring accurately for true
antimalarial drug resistance and promptly correcting sub-optimal dosage regimens
to prevent these contributing to the emergence and spread of antimalarial
resistance.