Pharmacokinetic and Pharmacodynamic Considerations in Antimalarial Dose Optimization
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...
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| Format: | Online |
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American Society for Microbiology
2013
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| Online Access: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3837842/ |
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pubmed-3837842 |
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pubmed-38378422013-12-05 Pharmacokinetic and Pharmacodynamic Considerations in Antimalarial Dose Optimization White, Nicholas J. Minireview 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 pharmacokinetic-pharmacodynamic (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. American Society for Microbiology 2013-12 /pmc/articles/PMC3837842/ /pubmed/24002099 http://dx.doi.org/10.1128/AAC.00287-13 Text en Copyright © 2013 White. http://creativecommons.org/licenses/by/3.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution 3.0 Unported license (http://creativecommons.org/licenses/by/3.0/) . |
| repository_type |
Open Access Journal |
| institution_category |
Foreign Institution |
| institution |
US National Center for Biotechnology Information |
| building |
NCBI PubMed |
| collection |
Online Access |
| language |
English |
| format |
Online |
| author |
White, Nicholas J. |
| spellingShingle |
White, Nicholas J. Pharmacokinetic and Pharmacodynamic Considerations in Antimalarial Dose Optimization |
| author_facet |
White, Nicholas J. |
| author_sort |
White, Nicholas J. |
| title |
Pharmacokinetic and Pharmacodynamic Considerations in Antimalarial Dose Optimization |
| title_short |
Pharmacokinetic and Pharmacodynamic Considerations in Antimalarial Dose Optimization |
| title_full |
Pharmacokinetic and Pharmacodynamic Considerations in Antimalarial Dose Optimization |
| title_fullStr |
Pharmacokinetic and Pharmacodynamic Considerations in Antimalarial Dose Optimization |
| title_full_unstemmed |
Pharmacokinetic and Pharmacodynamic Considerations in Antimalarial Dose Optimization |
| title_sort |
pharmacokinetic and pharmacodynamic considerations in antimalarial dose optimization |
| description |
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 pharmacokinetic-pharmacodynamic (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. |
| publisher |
American Society for Microbiology |
| publishDate |
2013 |
| url |
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3837842/ |
| _version_ |
1612030087377453056 |