Publication: Pharmacokinetic and pharmacodynamic considerations in antimalarial dose optimization
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Issued Date
2013-12-01
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ISSN
10986596
00664804
00664804
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2-s2.0-84887416507
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Mahidol University
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SCOPUS
Bibliographic Citation
Antimicrobial Agents and Chemotherapy. Vol.57, No.12 (2013), 5792-5807
Suggested Citation
Nicholas J. White Pharmacokinetic and pharmacodynamic considerations in antimalarial dose optimization. Antimicrobial Agents and Chemotherapy. Vol.57, No.12 (2013), 5792-5807. doi:10.1128/AAC.00287-13 Retrieved from: https://repository.li.mahidol.ac.th/handle/123456789/32063
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Title
Pharmacokinetic and pharmacodynamic considerations in antimalarial dose optimization
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Abstract
Antimalarial drugs have usually been first deployed in areas of malaria endemicity at doses which were too low, particularly for high-risk groups such as young children and pregnant women. This may accelerate the emergence and spread of resistance, thereby shortening the useful life of the drug, but it is an inevitable consequence of the current imprecise method of dose finding. An alternative approach to dose finding is suggested in which phase 2 studies concentrate initially on pharmacokineticpharmacodynamic (PK-PD) characterization and in vivo calibration of in vitro susceptibility information. PD assessment is facilitated in malaria because serial parasite densities are readily assessed by microscopy, and at low densities by quantitative PCR, so that initial therapeutic responses can be quantitated accurately. If the in vivo MIC could be characterized early in phase 2 studies, it would provide a sound basis for the choice of dose in all target populations in subsequent combination treatments. Population PK assessments in phase 2b and phase 3 studies which characterize PK differences between different age groups, clinical disease states, and human populations can then be combined with the PK-PD observations to provide a sound evidence base for dose recommendations in different target groups. Copyright © 2013 White.