Evidence map›Paper›PMID 22391528›Full record

ArticleAntimicrobial agents and chemotherapy2012

In vitro cardiovascular effects of dihydroartemisin-piperaquine combination compared with other antimalarials.

Franco Borsini, William Crumb, Silvia Pace, David Ubben, Barb Wible, Gan-Xin Yan, Christian Funck-Brentano

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

Article in Antimicrobial agents and chemotherapy, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers, 4 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
38citing papers in PubMed, 4 pooled it
2.7field-weighted citation impact, top 9% 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

38 citing papers in PubMed, 4 syntheses or guidelines pooled it, 64 citations in OpenAlex.

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  7. Piperaquine-Induced QTc Prolongation Decreases With Repeated Monthly Dihydroartemisinin-Piperaquine Dosing in Pregnant Ugandan Women.Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 2022
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  19. Population-specific variations inAntimicrobial agents and chemotherapy · 2024
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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

7 authors at 5 institutions in 4 countries.

Franco BorsiniSigma-Tau Industrie Farmaceutiche Riunite spa, Pomezia, Italy.
William Crumb
Silvia Pace
David Ubben
Barb Wible
Gan-Xin Yan
Christian Funck-Brentano
Sigma Tau (Italy) · ITAssistance Publique – Hôpitaux de Paris · FRLankenau Institute for Medical Research · USMedicines for Malaria Venture · CHWesTest Engineering (United States) · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

The in vitro cardiac properties of dihydroartemisinin (DHA) plus piperaquine phosphate (PQP) were compared with those of other antimalarial compounds. Results with antimalarial drugs, chosen on the basis of their free therapeutic maximum concentration in plasma (C(max)), were expressed as the fold of that particular effect with respect to their C(max). The following tests were used at 37 °C: hERG (human ether-à-go-go-related gene) blockade and trafficking, rabbit heart ventricular preparations, and sodium and slow potassium ion current interference (I(Na) and I(Ks), respectively). Chloroquine, halofantrine, mefloquine, and lumefantrine were tested in the hERG studies, but only chloroquine, dofetilide, lumefantrine, and the combination of artemether-lumefantrine were used in the rabbit heart ventricular preparations, hERG trafficking studies, and I(Na) and I(Ks) analyses. A proper reference was used in each test. In hERG studies, the high 50% inhibitory concentration (IC(50)) of halofantrine, which was lower than its C(max), was confirmed. All the other compounds blocked hERG, with IC(50)s ranging from 3- to 30-fold their C(max)s. In hERG trafficking studies, the facilitative effects of chloroquine at about 30-fold its C(max) were confirmed and DHA blocked it at a concentration about 300-fold its C(max). In rabbit heart ventricular preparations, dofetilide, used as a positive control, revealed a high risk of torsades de pointes, whereas chloroquine showed a medium risk. Neither DHA-PQP nor artemether-lumefantrine displayed an in vitro signal for a significant proarrhythmic risk. Only chloroquine blocked the I(Na) ion current and did so at about 30-fold its C(max). No effect on I(Ks) was detected. In conclusion, despite significant hERG blockade, DHA-PQP and artemether-lumefantrine do not appear to induce potential torsadogenic effects in vitro, affect hERG trafficking, or block sodium and slow potassium ion currents.

Indexed as

AnimalsAntimalarialsArtemisininsCell LineElectrophysiologyFemaleHeart VentriclesHumansIn Vitro TechniquesPiperazinesQuinolinesRabbitsAntimalarialsArtemisininsartenimolpiperaquinePiperazinesQuinolines

Identifiers

PMID22391528
PMCPMC3370756
OpenAlexW1981589246

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.