| Title |
Population pharmacokinetic and pharmacodynamic properties of artesunate in patients with artemisinin sensitive and resistant infections in Southern Myanmar
|
|---|---|
| Published in |
Malaria Journal, March 2018
|
| DOI | 10.1186/s12936-018-2278-5 |
| Pubmed ID | |
| Authors |
Jesmin Permala Lohy Das, Myat P. Kyaw, Myat H. Nyunt, Khin Chit, Kyin H. Aye, Moe M. Aye, Mats O. Karlsson, Martin Bergstrand, Joel Tarning |
| Abstract |
Artemisinins 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. Fifty-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. The 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. The 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. |
X Demographics
The data shown below were collected from the profiles of 3 X users who shared this research output. Click here to find out more about how the information was compiled.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 3 | 100% |
Demographic breakdown
| Type | Count | As % |
|---|---|---|
| Members of the public | 2 | 67% |
| Science communicators (journalists, bloggers, editors) | 1 | 33% |
Mendeley readers
The data shown below were compiled from readership statistics for 54 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 54 | 100% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Researcher | 11 | 20% |
| Student > Ph. D. Student | 8 | 15% |
| Student > Master | 6 | 11% |
| Student > Bachelor | 4 | 7% |
| Student > Doctoral Student | 2 | 4% |
| Other | 7 | 13% |
| Unknown | 16 | 30% |
| Readers by discipline | Count | As % |
|---|---|---|
| Medicine and Dentistry | 10 | 19% |
| Pharmacology, Toxicology and Pharmaceutical Science | 8 | 15% |
| Agricultural and Biological Sciences | 5 | 9% |
| Biochemistry, Genetics and Molecular Biology | 4 | 7% |
| Nursing and Health Professions | 4 | 7% |
| Other | 7 | 13% |
| Unknown | 16 | 30% |
Attention Score in Context
This research output has an Altmetric Attention Score of 1. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 05 February 2019.
All research outputs
#16,712,239
of 24,580,204 outputs
Outputs from Malaria Journal
#4,607
of 5,786 outputs
Outputs of similar age
#216,594
of 335,941 outputs
Outputs of similar age from Malaria Journal
#92
of 119 outputs
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