Evidence map›Paper›PMID 21876056›Full record

Trial reportAntimicrobial agents and chemotherapy2011

Population pharmacokinetics of artemether, lumefantrine, and their respective metabolites in Papua New Guinean children with uncomplicated malaria.

Sam Salman, Madhu Page-Sharp, Susan Griffin, Kaye Kose, Peter M Siba, Kenneth F Ilett, Ivo Mueller, Timothy M E Davis

Open access · bronzeAbstract readClinical Trial
PubMed Full text at PMC Publisher
In one paragraph

Trial report in Antimicrobial agents and chemotherapy, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers, 4 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
35citing papers in PubMed, 4 pooled it
3.8field-weighted citation impact, top 8% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

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.

2 · The registry

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.

3 · Its place in the literature

Who cites it

35 citing papers in PubMed, 4 syntheses or guidelines pooled it, 53 citations in OpenAlex.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

8 authors at 3 institutions in 2 countries.

Sam SalmanSchool of Medicine and Pharmacology, University of Western Australia, Fremantle Hospital, Fremantle, Western Australia, Australia.
Madhu Page-Sharp
Susan Griffin
Kaye Kose
Peter M Siba
Kenneth F Ilett
Ivo Mueller
Timothy M E Davis
Papua New Guinea Institute of Medical Research · PGFremantle Hospital · AUCurtin University · AU

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

There are sparse published data relating to the pharmacokinetic properties of artemether, lumefantrine, and their active metabolites in children, especially desbutyl-lumefantrine. We studied 13 Papua New Guinean children aged 5 to 10 years with uncomplicated malaria who received the six recommended doses of artemether (1.7 mg/kg of body weight) plus lumefantrine (10 mg/kg), given with fat over 3 days. Intensive blood sampling was carried out over 42 days. Plasma artemether, dihydroartemisinin, lumefantrine, and desbutyl-lumefantrine were assayed using liquid chromatography-mass spectrometry or high-performance liquid chromatography. Multicompartmental pharmacokinetic models for a drug plus its metabolite were developed using a population approach that included plasma artemether and dihydroartemisinin concentrations below the limit of quantitation. Although artemether bioavailability was variable and its clearance increased by 67.8% with each dose, the median areas under the plasma concentration-time curve from 0 h to infinity (AUC(0-∞)s) for artemether and dihydroartemisinin (3,063 and 2,839 μg · h/liter, respectively) were similar to those reported previously in adults with malaria. For lumefantrine, the median AUC(0-∞) (459,980 μg · h/liter) was also similar to that in adults with malaria. These data support the higher dose recommended for children weighing 15 to 35 kg (35% higher than that for a 50-kg adult) but question the recommendation for a lower dose in children weighing 12.5 to 15 kg. The median desbutyl-lumefantrine/lumefantrine ratio in the children in our study was 1.13%, within the range reported for adults and higher at later time points because of the longer desbutyl-lumefantrine terminal elimination half-life. A combined desbutyl-lumefantrine and lumefantrine AUC(0-∞) weighted on in vitro antimalarial activity was inversely associated with recurrent parasitemia, suggesting that both the parent drug and the metabolite contribute to the treatment outcome of artemether-lumefantrine.

Indexed as

AntimalarialsArtemetherArtemisininsChildChild, PreschoolEthanolaminesFemaleFluorenesHumansLumefantrineMalariaMaleAntimalarialsArtemetherArtemisininsEthanolaminesFluorenesLumefantrine

Identifiers

PMID21876056
PMCPMC3194999
OpenAlexW2033755024

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

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.