ArticleScience translational medicine2013
Model system to define pharmacokinetic requirements for antimalarial drug efficacy.
Article in Science translational medicine, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
23 citing papers in PubMed, 36 citations in OpenAlex.
- Chloroquine is grossly under dosed in young children with malaria: implications for drug resistance.PloS one · 2014Trial
- Translational Pharmacokinetic and Pharmacodynamic Evaluation of Mefloquine AgainstACS pharmacology & translational science · 2026Article
- RNA Polymerase 1 inhibitors against African trypanosomesAntimicrobial agents and chemotherapy · 2026Article
- Pharmacokinetics of venetoclax in a patient after whipple pancreaticoduodenectomy.Cancer chemotherapy and pharmacology · 2026Article
- Clinically relevant atovaquone-resistant human malaria parasites fail to transmit by mosquito.Nature communications · 2023Article
- Naturally Acquired Kelch13 Mutations in Plasmodium falciparum Strains ModulateMicrobiology spectrum · 2022Article
- Transcending Dimensions in Apicomplexan Research: from Two-Dimensional to Three-DimensionalMicrobiology and molecular biology reviews : MMBR · 2022Review
- Drug-Dependent Morphological Transitions in Spherical and Worm-Like Polymeric Micelles Define Stability and Pharmacological Performance of Micellar Drugs.Small (Weinheim an der Bergstrasse, Germany) · 2022Article
- The Artemiside-Artemisox-Artemisone-M1 Tetrad: Efficacies against Blood StagePharmaceutics · 2021Article
- Antimalarial Drug Resistance and Implications for the WHO Global Technical Strategy.Current epidemiology reports · 2021Review
- Modulation of Triple Artemisinin-Based Combination Therapy Pharmacodynamics byACS pharmacology & translational science · 2020Article
- Novel 2D and 3D Assays to Determine the Activity of Anti-Leishmanial Drugs.Microorganisms · 2020Article
- Kinetic Driver of Antibacterial Drugs againstAntimicrobial agents and chemotherapy · 2019Article
- Optimal kinetic exposures for classic and candidate antitrypanosomals.The Journal of antimicrobial chemotherapy · 2019Article
- Model System Identifies Kinetic Driver of Hsp90 Inhibitor Activity against African Trypanosomes and Plasmodium falciparum.Antimicrobial agents and chemotherapy · 2018Article
- Identification and characterization of the antiplasmodial activity of Hsp90 inhibitors.Malaria journal · 2017Article
- New developments in anti-malarial target candidate and product profiles.Malaria journal · 2017Review
- Comparative pharmacokinetics and pharmacodynamics of intravenous artelinate versus artesunate in uncomplicated Plasmodium coatneyi-infected rhesus monkey model.Malaria journal · 2016Article
- Hollow-Fiber Methodology for Pharmacokinetic/Pharmacodynamic Studies of Antimalarial Compounds.Current protocols in chemical biology · 2016Article
- Pharmacokinetic-pharmacodynamic analysis of spiroindolone analogs and KAE609 in a murine malaria model.Antimicrobial agents and chemotherapy · 2015Article
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
Malaria presents a tremendous public health burden, and new therapies are needed. Massive compound libraries screened against Plasmodium falciparum have yielded thousands of lead compounds, resulting in an acute need for rational criteria to select the best candidates for development. We reasoned that, akin to antibacterials, antimalarials might have an essential pharmacokinetic requirement for efficacy: action governed either by total exposure or peak concentration (AUC/CMAX), or by duration above a defined minimum concentration [time above minimum inhibitory concentration (TMIC)]. We devised an in vitro system for P. falciparum, capable of mimicking the dynamic fluctuations of a drug in vivo. Using this apparatus, we find that chloroquine is TMIC-dependent, whereas the efficacy of artemisinin is driven by CMAX. The latter was confirmed in a mouse model of malaria. These characteristics can explain the clinical success of two antimalarial drugs with widely different kinetics in humans. Chloroquine, which persists for weeks, is ideally suited for its TMIC mechanism, whereas great efficacy despite short exposure (t1/2 in blood 3 hours or less) is attained by CMAX-driven artemisinins. This validated preclinical model system can be used to select those antimalarial lead compounds whose CMAX or TMIC requirement for efficacy matches pharmacokinetics obtained in vivo. The apparatus can also be used to explore the kinetic dependence of other pharmacodynamic endpoints in parasites.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.