Evidence map›Paper›PMID 25047305›Full record

Trial reportMalaria journal2014

Pharmacokinetic evaluation of intravenous artesunate in adults with uncomplicated falciparum malaria in Kenya: a phase II study.

Qigui Li, Shon Remich, Scott R Miller, Bernhards Ogutu, Walter Otieno, Victor Melendez, Paktiya Teja-Isavadharm, Peter J Weina, Mark R Hickman, Bryan Smith and 1 more

Open access · goldAbstract readClinical Trial, Phase II
In one paragraph

Trial report in Malaria journal, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.

0numbers the graph read from it
0cells of the map it votes in
7citing papers in PubMed
1.0field-weighted citation impact, top 20% 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

7 citing papers in PubMed, 15 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

11 authors at 3 institutions in 3 countries.

Qigui LiDivision of Experimental Therapeutics, Walter Reed Army Institute of Research (WRAIR), 503 Robert Grant Avenue, Silver Spring, MD, 20910-7500, USA. qigui.li.civ@mail.mil.
Shon Remich
Scott R Miller
Bernhards Ogutu
Walter Otieno
Victor Melendez
Paktiya Teja-Isavadharm
Peter J Weina
Mark R Hickman
Bryan Smith
Mark Polhemus
Walter Reed Army Institute of Research · USUnited States Army Medical Research Directorate - Africa · KEArmed Forces Research Institute of Medical Science · TH

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundAlternatives to treatment for malaria treatment of travellers are needed in the USA and in Europe for travellers who return with severe malaria infections. The objective of this study is to show the pharmacokinetic (PK) profile of intravenous artesunate (AS), which was manufactured under good manufacturing practice (GMP) conditions, in adults with uncomplicated falciparum malaria in Kenya.

methodsThe PK parameters of intravenous AS manufactured under current cGMP were evaluated after a single dose of drug at 2.4 mg/kg infused over 2 min in 28 adults with uncomplicated Plasmodium falciparum malaria. Plasma concentrations of AS and dihydroartemisinin (DHA) were measured using a validated liquid chromatography-mass spectrometry (LC-MS/MS) methodology. Pharmacokinetic data were analysed with a compartmental analysis for AS and DHA.

resultsThe results suggest there were no drug-related adverse events in any of the patients. After intravenous infusion, the concentration of the parent drug rapidly declined, and the AS was converted to DHA. AS and DHA showed mean elimination half-lives of 0.17 hours and 1.30 hours, respectively. The high mean peak concentration (Cmax) of AS was shown to be 28,558 ng/mL while the Cmax of DHA was determined to be 2,932 ng/mL. Significant variability was noted in the PK profiles of the 28 patients tested. For example, Cmax values of AS were calculated to range from 3,362 to 55,873 ng/mL, and the Cmax value of DHA was noted to vary from 1,493 to 5,569 ng/mL. The mean area under the curve (AUC) of AS was shown to be approximately half that of DHA (1,878 ng · h/mL vs 3,543 ng · h/mL). The DHA/AS ratio observed was 1.94 during the one-day single treatment, and the AUC and half- life measured for DHA were significantly larger and longer than for AS.

conclusionsIntravenous AS can provide much higher peak concentrations of AS when compared to concentrations achieved with oral therapy; this may be crucial for the rapid elimination of parasites in patients with severe malaria. Given the much longer half-life of DHA compared to the short half-life of AS, DHA also plays a significant role in treatment of severe malaria.

Indexed as

Activation, MetabolicAdultAgedAntimalarialsArtemisininsArtesunateAtovaquoneChromatography, LiquidDrug CombinationsDrug CompoundingDrug MonitoringFemaleHalf-LifeHumansInfusions, IntravenousKenyaAntimalarialsArtemisininsartenimolArtesunateAtovaquoneatovaquone, proguanil drug combinationDrug CombinationsProguanil

Identifiers

PMID25047305
PMCPMC4112823
OpenAlexW2097175233

What OpenQuestion holds

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LicenceCC BY
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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.