Evidence map›Paper›PMID 24867986›Full record

ArticleAntimicrobial agents and chemotherapy2014

Population pharmacokinetics and clinical response for artemether-lumefantrine in pregnant and nonpregnant women with uncomplicated Plasmodium falciparum malaria in Tanzania.

Dominic Mosha, Monia Guidi, Felista Mwingira, Salim Abdulla, Thomas Mercier, Laurent Arthur Decosterd, Chantal Csajka, Blaise Genton

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

Article in Antimicrobial agents and chemotherapy, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers, 8 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
31citing papers in PubMed, 8 pooled it
6.1field-weighted citation impact, top 4% 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

31 citing papers in PubMed, 8 syntheses or guidelines pooled it, 41 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 4 institutions in 2 countries.

Dominic MoshaIfakara Health Institute, Rufiji Health Demographic Surveillance System (HDSS), Rufiji, Tanzania Swiss Tropical and Public Health Institute, University of Basel, Basel, Switzerland dfmosha@hotmail.com.
Monia GuidiSchool of Pharmaceutical Sciences, University of Geneva, University of Lausanne, Lausanne, Switzerland Division of Clinical Pharmacology and Toxicology, Department of Laboratories, Centre Hospitalier Universitaire Vaudois and University of Lausanne, Lausanne, Switzerland.
Felista MwingiraSwiss Tropical and Public Health Institute, University of Basel, Basel, Switzerland.
Salim AbdullaIfakara Health Institute, Rufiji Health Demographic Surveillance System (HDSS), Rufiji, Tanzania.
Thomas MercierDivision of Clinical Pharmacology and Toxicology, Department of Laboratories, Centre Hospitalier Universitaire Vaudois and University of Lausanne, Lausanne, Switzerland.
Laurent Arthur DecosterdDivision of Clinical Pharmacology and Toxicology, Department of Laboratories, Centre Hospitalier Universitaire Vaudois and University of Lausanne, Lausanne, Switzerland.
Chantal CsajkaSchool of Pharmaceutical Sciences, University of Geneva, University of Lausanne, Lausanne, Switzerland Division of Clinical Pharmacology and Toxicology, Department of Laboratories, Centre Hospitalier Universitaire Vaudois and University of Lausanne, Lausanne, Switzerland.
Blaise GentonSwiss Tropical and Public Health Institute, University of Basel, Basel, Switzerland Department of Ambulatory Care and Community Medicine and Division of Infectious Diseases, University Hospital, Lausanne, Switzerland.
University of Lausanne · CHIfakara Health Institute · TZUniversity of Basel · CHUniversity of Geneva · CH

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Artemether-lumefantrine (AL) is the first-line treatment for uncomplicated malaria in the second and third trimesters of pregnancy. Its efficacy during pregnancy has recently been challenged due to altered pharmacokinetic (PK) properties in this vulnerable group. The aim of this study was to determine the PK profile of AL in pregnant and nonpregnant women and assess their therapeutic outcome. Thirty-three pregnant women and 22 nonpregnant women with malaria were treated with AL (80/480 mg) twice daily for 3 days. All patients provided five venous plasma samples for drug quantification at random times over 7 days. Inter- and intraindividual variability was assessed, and the effects of covariates were quantified using a nonlinear mixed-effects modeling approach (NONMEM). A one-compartment model with first-order absorption and elimination with linear metabolism from drug to metabolite fitted the data best for both arthemether (AM) and lumefantrine (LF) and their metabolites. Pregnancy status and diarrhea showed a significant influence on LF PK. The relative bioavailability of lumefantrine and its metabolism rate into desmethyl-lumefantrine were, respectively, 34% lower and 78% higher in pregnant women than in nonpregnant patients. The overall PCR-uncorrected treatment failure rates were 18% in pregnant women and 5% in nonpregnant women (odds ratio [OR] = 4.04; P value of 0.22). A high median day 7 lumefantrine concentration was significantly associated with adequate clinical and parasitological response (P = 0.03). The observed reduction in the relative bioavailability of lumefantrine in pregnant women may explain the higher treatment failure in this group, mostly due to lower posttreatment prophylaxis. Hence, a modified treatment regimen of malaria in pregnancy should be considered.

Indexed as

Models, StatisticalAdolescentAdultAntimalarialsArtemether, Lumefantrine Drug CombinationArtemisininsBiological AvailabilityBiotransformationCase-Control StudiesDrug Administration ScheduleDrug CombinationsEthanolaminesFemaleFluorenesHumansMalaria, FalciparumAntimalarialsArtemether, Lumefantrine Drug CombinationArtemisininsDrug CombinationsEthanolaminesFluorenes

Identifiers

PMID24867986
PMCPMC4136066
OpenAlexW2152305350

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.