Evidence map›Paper›PMID 19564366›Full record

Trial reportAntimicrobial agents and chemotherapy2009

Population pharmacokinetics of lumefantrine in pregnant women treated with artemether-lumefantrine for uncomplicated Plasmodium falciparum malaria.

Joel Tarning, Rose McGready, Niklas Lindegardh, Elizabeth A Ashley, Mupawjay Pimanpanarak, Benjamas Kamanikom, Anna Annerberg, Nicholas P J Day, Kasia Stepniewska, Pratap Singhasivanon and 2 more

Abstract readRandomized Controlled Trial
PubMed Full text at PMC Publisher
In one paragraph

Trial report in Antimicrobial agents and chemotherapy, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 62 papers, 7 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
62citing papers in PubMed, 7 pooled it
11.8field-weighted citation impact, top 1% 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

62 citing papers in PubMed, 7 syntheses or guidelines pooled it, 101 citations in OpenAlex.

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2 more citing papers are in PubMed but not listed here.

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

12 authors at 4 institutions in 2 countries.

Joel TarningMahidol-Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand. joel@tropmedres.ac
Rose McGready
Niklas Lindegardh
Elizabeth A Ashley
Mupawjay Pimanpanarak
Benjamas Kamanikom
Anna Annerberg
Nicholas P J Day
Kasia Stepniewska
Pratap Singhasivanon
Nicholas J White
François Nosten
Mahidol University · THChurchill Hospital · GBMahidol Oxford Tropical Medicine Research Unit · THShoklo Malaria Research Unit · TH

Funding

Wellcome Trust
6 · The paper itself

Abstract

Artemether-lumefantrine has become one of the most widely used antimalarial drugs in the world. The objective of this study was to determine the population pharmacokinetic properties of lumefantrine in pregnant women with uncomplicated multidrug-resistant Plasmodium falciparum malaria on the northwestern border of Thailand. Burmese and Karen women (n = 103) with P. falciparum malaria and in the second and third trimesters of pregnancy were treated with artemether-lumefantrine (80/480 mg) twice daily for 3 days. All patients provided five capillary plasma samples for drug quantification, and the collection times were randomly distributed over 14 days. The concentration-time profiles of lumefantrine were assessed by nonlinear mixed-effects modeling. The treatment failure rate (PCR-confirmed recrudescent infections at delivery) was high; 16.5% (95% confidence interval, 9.9 to 25.1). The population pharmacokinetics of lumefantrine were described well by a two-compartment open model with first-order absorption and elimination. The final model included interindividual variability in all pharmacokinetic parameters and a linear covariate relationship between the estimated gestational age and the central volume of distribution. A high proportion of all women (40%, 41/103) had day 7 capillary plasma concentrations of <355 ng/ml (which corresponds to approximately <280 ng/ml in venous plasma), a threshold previously associated with an increased risk of therapeutic failure in nonpregnant patients in this area. Predictive modeling suggests that a twice-daily regimen given for 5 days would be preferable in later pregnancy. In conclusion, altered pharmacokinetic properties of lumefantrine contribute to the high rates of failure of artemether-lumefantrine treatment in later pregnancy. Dose optimization is urgently needed.

Indexed as

AdolescentAdultAnimalsAntimalarialsArtemetherArtemisininsEthanolaminesFemaleFluorenesHumansLogistic ModelsLumefantrineMalaria, FalciparumPregnancyYoung AdultAntimalarialsArtemetherArtemisininsEthanolaminesFluorenesLumefantrine

Identifiers

PMID19564366
PMCPMC2737887
OpenAlexW2142803342

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.