Trial reportBritish journal of clinical pharmacology2005
Semi-mechanistic pharmacokinetic/pharmacodynamic modelling of the antimalarial effect of artemisinin.
Trial report in British journal of clinical pharmacology, 2005. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
What it found
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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.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
22 citing papers in PubMed, 46 citations in OpenAlex.
- Opposite malaria and pregnancy effect on oral bioavailability of artesunate - a population pharmacokinetic evaluation.British journal of clinical pharmacology · 2015Trial
- Pharmacokinetic comparison of two piperaquine-containing artemisinin combination therapies in Papua New Guinean children with uncomplicated malaria.Antimicrobial agents and chemotherapy · 2012Trial
- Population pharmacokinetics and pharmacodynamics of artemether and lumefantrine during combination treatment in children with uncomplicated falciparum malaria in Tanzania.Antimicrobial agents and chemotherapy · 2010Trial
- Uncertainty undermines the validity of antimicrobial pharmacodynamics.Journal of pharmacokinetics and pharmacodynamics · 2026Article
- An artesunate pharmacometric model to explain therapeutic responses in falciparum malaria.The Journal of antimicrobial chemotherapy · 2023Article
- Effect of autoinduction and food on the pharmacokinetics of furmonertinib and its active metabolite characterized by a population pharmacokinetic model.Acta pharmacologica Sinica · 2022Article
- Population Pharmacokinetics of Antimalarial Naphthoquine in Combination with Artemisinin in Tanzanian Children and Adults: Dose Optimization.Antimicrobial agents and chemotherapy · 2022Article
- Transitioning from Basic toward Systems Pharmacodynamic Models: Lessons from Corticosteroids.Pharmacological reviews · 2020Review
- Optimal Treatments for Severe Malaria and the Threat Posed by Artemisinin Resistance.The Journal of infectious diseases · 2019Article
- Split dosing of artemisinins does not improve antimalarial therapeutic efficacy.Scientific reports · 2017Article
- Malaria parasite clearance.Malaria journal · 2017Review
- Incorporating Stage-Specific Drug Action into Pharmacological Modeling of Antimalarial Drug Treatment.Antimicrobial agents and chemotherapy · 2016Article
- Rethinking Dosing Regimen Selection of Piperaquine for Malaria Chemoprevention: A Simulation Study.PloS one · 2016Article
- How Robust Are Malaria Parasite Clearance Rates as Indicators of Drug Effectiveness and Resistance?Antimicrobial agents and chemotherapy · 2015Article
- Targeting the cell stress response of Plasmodium falciparum to overcome artemisinin resistance.PLoS biology · 2015Article
- Modelling the time course of antimalarial parasite killing: a tour of animal and human models, translation and challenges.British journal of clinical pharmacology · 2015Review
- Making the most of clinical data: reviewing the role of pharmacokinetic-pharmacodynamic models of anti-malarial drugs.The AAPS journal · 2014Review
- Moving from basic toward systems pharmacodynamic models.Journal of pharmaceutical sciences · 2013Review
- Mechanism-based model of parasite growth and dihydroartemisinin pharmacodynamics in murine malaria.Antimicrobial agents and chemotherapy · 2013Article
- Population pharmacokinetics of fusidic acid: rationale for front-loaded dosing regimens due to autoinhibition of clearance.Antimicrobial agents and chemotherapy · 2013Article
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Authors and funding
3 authors at 2 institutions in 2 countries.
Funding
Abstract
purposeTo characterize artemisinin pharmacokinetics (PK) and its antimalarial activity in vivo.
methodsArtemisinin salivary concentration and parasite count data were obtained from Vietnamese malaria patients receiving two different dosage regimens. PK data were analysed using a previously developed semiphysiological model incorporating autoinduction of eliminating enzymes. A pharmacodynamic (PD) model reflecting different stages of the parasite life-cycle was developed and fitted to the data. The model included visible and invisible compartments as well as sensitive, insensitive, and injured parasite stages. Salivary artemisinin concentrations functioned as the driving force for the observed decrease in the number of parasites.
resultsLarge interindividual variability was observed in both PK and PD data. The PK model described reasonably well the observed decrease in salivary concentrations after repeated drug administration. The preinduction hepatic extraction ratio of artemisinin was estimated to be 0.87 with a volume of distribution of 27 L. Artemisinin half-life averaged 0.7 h. Incorporation of a saturable hepatic elimination affecting the first-pass extraction as well as a higher intrinsic clearance in female patients resulted in the best fit of the model to the data. The PD model described the decrease in the number of parasites during the course of treatment well. The longest mean transit time of parasites from sensitive, visible to invisible to insensitive visible stages was found to be 34.5 h through one life-cycle. The half-life of injured parasites was 2.7 h.
conclusionsThe proposed semimechanistic PK/PD model successfully described the time course of both salivary artemisinin concentrations after repeated dosing and the number of parasites in patients treated with the drug.
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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.