Trial reportMalaria journal2018
Population pharmacokinetic and pharmacodynamic properties of artesunate in patients with artemisinin sensitive and resistant infections in Southern Myanmar.
Trial report in Malaria journal, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
11 citing papers in PubMed, 17 citations in OpenAlex.
- Population pharmacokinetics and pharmacodynamics of the artesunate-mefloquine fixed dose combination for the treatment of uncomplicated falciparum malaria in African children.Malaria journal · 2019Trial
- Pharmacokinetics and Pharmacodynamics of Antimalarial Agents: Optimizing Combination Therapies to Overcome Resistance Mechanisms.Journal of clinical pharmacology · 2026Review
- Safety, tolerability and pharmacokinetic properties of intranasal artesunate in a first in human phase 1 trial.Scientific reports · 2026Article
- Article
- Article
- Safety and PCR monitoring in 161 semi-immune Kenyan adults following controlled human malaria infection.JCI insight · 2021Article
- Development and Validation of anAntimicrobial agents and chemotherapy · 2021Article
- Population Pharmacokinetics and Pharmacodynamics of Chloroquine in a Plasmodium vivax Volunteer Infection Study.Clinical pharmacology and therapeutics · 2020Article
- Prior information for population pharmacokinetic and pharmacokinetic/pharmacodynamic analysis: overview and guidance with a focus on the NONMEM PRIOR subroutine.Journal of pharmacokinetics and pharmacodynamics · 2020Review
- Development of visual predictive checks accounting for multimodal parameter distributions in mixture models.Journal of pharmacokinetics and pharmacodynamics · 2019Article
- Susceptibility of Plasmodium falciparum to artemisinins and Plasmodium vivax to chloroquine in Phuoc Chien Commune, Ninh Thuan Province, south-central Vietnam.Malaria journal · 2019Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors at 3 institutions in 3 countries.
Funding
Abstract
backgroundArtemisinins are the most effective anti-malarial drugs for uncomplicated and severe Plasmodium falciparum malaria. However, widespread artemisinin resistance in the Greater Mekong Region of Southeast Asia is threatening the possibility to control and eliminate malaria. This work aimed to evaluate the pharmacokinetic and pharmacodynamic properties of artesunate and its active metabolite, dihydroartemisinin, in patients with sensitive and resistant falciparum infections in Southern Myanmar. In addition, a simple nomogram previously developed to identify artemisinin resistant malaria infections was evaluated.
methodsFifty-three (n = 53) patients were recruited and received daily oral artesunate monotherapy (4 mg/kg) for 7 days. Frequent artesunate and dihydroartemisinin plasma concentration measurements and parasite microscopy counts were obtained and evaluated using nonlinear mixed-effects modelling.
resultsThe absorption of artesunate was best characterized by a transit-compartment (n = 3) model, followed by one-compartment disposition models for artesunate and dihydroartemisinin. The drug-dependent parasite killing effect of dihydroartemisinin was described using an Emax function, with a mixture model discriminating between artemisinin sensitive and resistant parasites. Overall, 56% of the studied population was predicted to have resistant malaria infections. Application of the proposed nomogram to identify artemisinin-resistant malaria infections demonstrated an overall sensitivity of 90% compared to 55% with the traditional day-3 positivity test.
conclusionThe pharmacokinetic-pharmacodynamic properties of artesunate and dihydroartemisinin were well-characterized with a mixture model to differentiate between drug sensitive and resistant infections in these patients. More than half of all patients recruited in this study had artemisinin-resistant infections. The relatively high sensitivity of the proposed nomogram highlights its potential clinical usefulness.
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