Evidence map›Paper›PMID 18415093›Full record

Trial reportEuropean journal of clinical pharmacology2008

Pharmacokinetics and tolerability of artesunate and amodiaquine alone and in combination in healthy volunteers.

Catherine Orrell, Francesca Little, Peter Smith, Peter Folb, Walter Taylor, Piero Olliaro, Karen I Barnes

Open access · hybridAbstract readRandomized Controlled Trial
PubMed Full text at PMC Publisher
In one paragraph

Trial report in European journal of clinical pharmacology, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
49citing papers in PubMed, 1 pooled it
9.8field-weighted citation impact, top 2% 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

49 citing papers in PubMed, 1 synthesis or guideline pooled it, 90 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

7 authors at 3 institutions in 3 countries.

Catherine OrrellDivision of Clinical Pharmacology, Department of Medicine, University of Cape Town, Anzio Road, Observatory, Cape Town, 7925, South Africa.
Francesca Little
Peter Smith
Peter Folb
Walter Taylor
Piero Olliaro
Karen I Barnes
University of Cape Town · ZAUnited Nations Children's Fund India · INWorld Health Organization · CH

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

objectivesThe WHO recommends artemisinin-based combination therapies for treatment of uncomplicated falciparum malaria. At least 15 African countries have adopted artesunate plus amodiaquine as treatment policy. As no pharmacokinetic data on this combination have been published to date, we investigated its pharmacokinetic interactions and tolerability in healthy volunteers in Africa.

methodsIn a randomized, three-phase, cross-over study, amodiaquine (10 mg/kg) and artesunate (4 mg/kg) were given as single oral doses to 15 healthy volunteers. Artesunate was given to all volunteers on day 0. On day 7 they received either amodiaquine or amodiaquine plus artesunate and the alternative regimen on day 28. The pharmacokinetics of artesunate and amodiaquine and their main active metabolites dihydroartemisinin and desethylamodiaquine were compared following monotherapy and combination therapy using analysis of variance.

resultsThirteen volunteers completed the study, and pharmacokinetic parameters could be determined for twelve volunteers. When given in combination, the mean AUC was lower for dihydroartemisinin [ratio 67% (95% CI 51-88%); P = 0.008] and desethylamodiaquine [ratio 65% (95% CI 46-90%); P = 0.015] when compared with monotherapy. Adverse events of concern occurred in four volunteers (27%): grade 3 transaminitis (n = 1), neutropaenia (n = 2), and hypersensitivity (n = 1).

conclusionThe total drug exposure to both drugs was reduced significantly when they were given in combination. The clinical significance of these interactions is unclear and must be studied in malaria patients. The frequency and nature of adverse events among the healthy volunteers were of concern, and suggest laboratory monitoring would be needed in malaria patients treated with artesunate plus amodiaquine.

Indexed as

AdultAmodiaquineAntimalarialsArea Under CurveArtemisininsArtesunateCross-Over StudiesDrug Therapy, CombinationFemaleHumansMaleAmodiaquineAntimalarialsArtemisininsArtesunate

Identifiers

PMID18415093
PMCPMC2426925
OpenAlexW2110456860

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.