ArticleAntimicrobial agents and chemotherapy2016
Incorporating Stage-Specific Drug Action into Pharmacological Modeling of Antimalarial Drug Treatment.
Article in Antimicrobial agents and chemotherapy, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 28 citations in OpenAlex.
- Classification of outcomes in antimalarial therapeutic efficacy studies with Aster.Antimicrobial agents and chemotherapy · 2026Article
- Classification of outcomes in antimalarial therapeutic efficacy studies with Aster.bioRxiv : the preprint server for biology · 2025Article
- Antimalarial effect of synthetic endoperoxide on synchronized Plasmodium chabaudi infected mice.Parasites, hosts and diseases · 2023Article
- Parasite Viability as a Measure ofAntimicrobial agents and chemotherapy · 2022Article
- Article
- Optimizing bulk segregant analysis of drug resistance usingiScience · 2022Article
- Optimal control analysis of hepatocytic-erythrocytic dynamics ofInfectious Disease Modelling · 2022Article
- Non-invasive monitoring of drug action: A new live in vitro assay design for Chagas' disease drug discovery.PLoS neglected tropical diseases · 2020Article
- Whole-Cell Phenotypic Screening of Medicines for Malaria Venture Pathogen Box Identifies Specific Inhibitors ofAntimicrobial agents and chemotherapy · 2020Article
- Quantum Chemical Lipophilicities of Antimalarial Drugs in Relation to Terminal Half-Life.ACS omega · 2020Article
- Improving Methods for Analyzing Antimalarial Drug Efficacy Trials: Molecular Correction Based on Length-Polymorphic MarkersAntimicrobial agents and chemotherapy · 2019Article
- Optimal Treatments for Severe Malaria and the Threat Posed by Artemisinin Resistance.The Journal of infectious diseases · 2019Article
- Article
- Investigating the Efficacy of Triple Artemisinin-Based Combination Therapies for Treating Plasmodium falciparum Malaria Patients Using Mathematical Modeling.Antimicrobial agents and chemotherapy · 2018Article
- A Dynamic Stress Model Explains the Delayed Drug Effect in Artemisinin Treatment of Plasmodium falciparum.Antimicrobial agents and chemotherapy · 2017Article
- Quantifying the pharmacology of antimalarial drug combination therapy.Scientific reports · 2016Article
- OptiMal-PK: an internet-based, user-friendly interface for the mathematical-based design of optimized anti-malarial treatment regimens.Malaria journal · 2016Article
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Pharmacological modeling of antiparasitic treatment based on a drug's pharmacokinetic and pharmacodynamic properties plays an increasingly important role in identifying optimal drug dosing regimens and predicting their potential impact on control and elimination programs. Conventional modeling of treatment relies on methods that do not distinguish between parasites at different developmental stages. This is problematic for malaria parasites, as their sensitivity to drugs varies substantially during their 48-h developmental cycle. We investigated four drug types (short or long half-lives with or without stage-specific killing) to quantify the accuracy of the standard methodology. The treatment dynamics of three drug types were well characterized with standard modeling. The exception were short-half-life drugs with stage-specific killing (i.e., artemisinins) because, depending on time of treatment, parasites might be in highly drug-sensitive stages or in much less sensitive stages. We describe how to bring such drugs into pharmacological modeling by including additional variation into the drug's maximal killing rate. Finally, we show that artemisinin kill rates may have been substantially overestimated in previous modeling studies because (i) the parasite reduction ratio (PRR) (generally estimated to be 10(4)) is based on observed changes in circulating parasite numbers, which generally overestimate the "true" PRR, which should include both circulating and sequestered parasites, and (ii) the third dose of artemisinin at 48 h targets exactly those stages initially hit at time zero, so it is incorrect to extrapolate the PRR measured over 48 h to predict the impact of doses at 48 h and later.
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