Evidence map›Paper›PMID 40855460›Full record

ArticleTropical medicine and health2025

Physiologically based pharmacokinetic modelling to predict artemether and lumefantrine exposure in neonates weighing less than 5 kg treated with artemether-lumefantrine to supplement the clinical data from the CALINA study.

Helen Gu, Nada Abla, Vinay Kumar Venishetty, Birgit Schoeberl, Julia Zack, Heidi J Einolf

Registry-linked trialAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Tropical medicine and health, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT04300309 (Multicenter, Open-label, Single-arm Study to Evaluate the PK, Safety, Tolerability and Efficacy of a New Artemether), which is not on this map. Cited by 2 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed, 1 pooled it
–field-weighted citation impact
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.

NCT04300309 phase2 / phase3terminatednot on this map

Multicenter, Open-label, Single-arm Study to Evaluate the PK, Safety, Tolerability and Efficacy of a New Artemether:Lumefantrine (2.5 mg:30 mg) Dispersible Tablet in the Treatment of Infants and Neonates <5 kg Body Weight With Acute Uncomplicated Plasmodium Falciparum Malaria

TypeinterventionalSponsorNovartis PharmaceuticalsRan2020 to 2024Enrolled28ConditionsPlasmodium Falciparum MalariaArmsartemether:lumefantrine (2.5 mg:30 mg)
3 · Its place in the literature

Who cites it

2 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
  2. Article
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

6 authors.

Helen GuNovartis Pharmaceuticals Corporation, One Health Plaza, East Hanover, NJ, 07936-1080, USA. helen.gu@novartis.com.
Nada AblaMMV Medicines for Malaria Venture, Geneva, Switzerland.
Vinay Kumar VenishettyNovartis Healthcare Private Limited, Biomedical Research, Hyderabad, India.
Birgit SchoeberlNovartis Institutes for Biomedical Research, Cambridge, MA, USA.
Julia ZackNovartis Pharmaceuticals Corporation, One Health Plaza, East Hanover, NJ, 07936-1080, USA.
Heidi J EinolfNovartis Pharmaceuticals Corporation, One Health Plaza, East Hanover, NJ, 07936-1080, USA.

Funding

Novartis/Medicines for Malaria Venture/PAMAfrica consortium/European & Developing Countries Clinical Trials Partnership RIA2018SD-2306
6 · The paper itself

Abstract

backgroundEvidence-based recommendations for malaria treatment in patients weighing < 5 kg are lacking as a consequence of differences in pharmacokinetics due to age and/or body weight (BW), and recruitment challenges in conducting trials in this population. A physiologically based pharmacokinetic (PBPK) model was developed and validated to predict artemether and lumefantrine concentrations in patients < 5 kg BW aged 1-28 days. The model predictions supplemented data from a trial (CALINA; NCT04300309) with an optimized dose of artemether-lumefantrine (5 mg artemether: 60 mg lumefantrine) in patients < 5 kg with Plasmodium falciparum malaria.

methodsPBPK models of artemether and lumefantrine were developed using Simcyp (Version 22) and validation was performed using historical data from adults and paediatric patients. To compare model-predicted and observed values, populations were matched to clinical trial populations (ranging from adults to infants) for patient numbers and demographics. The models were applied to predict artemether maximal concentration (C

resultsValidated models for artemether and lumefantrine were used to predict plasma concentrations in neonates and young infants with BW < 5 kg after 3-day administration of 5 mg artemether and 60 mg lumefantrine twice daily with high confidence. The PBPK model using Upreti hepatic cytochrome P450 (CYP)3A4 ontogeny predicted observed artemether and lumefantrine exposure in infants and neonates better than Salem ontogeny. The predicted variability in neonates was comparable to or larger than the variability of observed concentrations in infants and older neonates in the CALINA study.

conclusionsBased on the success of the PBPK models for artemether and lumefantrine in predicting drug concentrations in adults and children, including neonates, modelling and simulation results can be used with confidence to supplement the limited available data for neonates (1-28 days old) < 5 kg BW obtained from the CALINA study for this rarer and more difficult to recruit patient population.

Indexed as

Artemether–lumefantrineCytochrome P450 CYP3A4 ontogenyFalciparum malariaNeonatal malariaPhysiologically based pharmacokinetic modellingSimcyp

Identifiers

PMID40855460
PMCPMC12376358

What Socratic holds

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Registered trials

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 Socratic graph.