Evidence map›Paper›PMID 22316571›Full record

Trial reportThe Journal of antimicrobial chemotherapy2012

Lopinavir/ritonavir significantly influences pharmacokinetic exposure of artemether/lumefantrine in HIV-infected Ugandan adults.

Pauline Byakika-Kibwika, Mohammed Lamorde, Violet Okaba-Kayom, Harriet Mayanja-Kizza, Elly Katabira, Warunee Hanpithakpong, Nadine Pakker, Thomas P C Dorlo, Joel Tarning, Niklas Lindegardh and 4 more

Open access · bronzeAbstract readClinical Trial
In one paragraph

Trial report in The Journal of antimicrobial chemotherapy, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers, 3 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
27citing papers in PubMed, 3 pooled it
3.2field-weighted citation impact, top 8% 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

27 citing papers in PubMed, 3 syntheses or guidelines pooled it, 55 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

14 authors at 9 institutions in 5 countries.

Pauline Byakika-KibwikaInfectious Diseases Institute, Makerere University, Kampala, Uganda. pbyakika@idi.co.ug
Mohammed Lamorde
Violet Okaba-Kayom
Harriet Mayanja-Kizza
Elly Katabira
Warunee Hanpithakpong
Nadine Pakker
Thomas P C Dorlo
Joel Tarning
Niklas Lindegardh
Peter J de Vries
David Back
Saye Khoo
Concepta Merry
Infectious Diseases Research Collaboration · UGMahidol Oxford Tropical Medicine Research Unit · THTrinity College Dublin · IEUniversity of Liverpool · GBAcademic Medical Center · NLInfectious Diseases Institute · UGMakerere University · UGThe Netherlands Cancer Institute · NLUniversity of Oxford · GB

Funding

Medical Research Council G0901364Wellcome Trust 077166/Z/05/ZWellcome Trust 089275
6 · The paper itself

Abstract

backgroundTreatment of HIV/malaria-coinfected patients with antiretroviral therapy (ART) and artemisinin-based combination therapy has potential for drug interactions. We investigated the pharmacokinetics of artemether, dihydroartemisinin and lumefantrine after administration of a single dose of 80/480 mg of artemether/lumefantrine to HIV-infected adults, taken with and without lopinavir/ritonavir.

methodsA two-arm parallel study of 13 HIV-infected ART-naive adults and 16 HIV-infected adults stable on 400/100 mg of lopinavir/ritonavir plus two nucleoside reverse transcriptase inhibitors (ClinicalTrials.gov, NCT 00619944). Each participant received a single dose of 80/480 mg of artemether/lumefantrine under continuous cardiac function monitoring. Plasma concentrations of artemether, dihydroartemisinin and lumefantrine were measured.

resultsCo-administration of artemether/lumefantrine with lopinavir/ritonavir significantly reduced artemether maximum concentration (C(max)) and area under the concentration-time curve (AUC) [median (range): 112 (20-362) versus 56 (17-236) ng/mL, P = 0.03; and 264 (92-1129) versus 151 (38-606) ng · h/mL, P < 0.01]. Dihydroartemisinin C(max) and AUC were not affected [66 (10-111) versus 73 (31-224) ng/mL, P = 0.55; and 213 (68-343) versus 175 (118-262) ng · h/mL P = 0.27]. Lumefantrine C(max) and AUC increased during co-administration [2532 (1071-5957) versus 7097 (2396-9462) ng/mL, P < 0.01; and 41,119 (12,850-125,200) versus 199,678 (71,205-251,015) ng · h/mL, P < 0.01].

conclusionsCo-administration of artemether/lumefantrine with lopinavir/ritonavir significantly increases lumefantrine exposure, but decreases artemether exposure. Population pharmacokinetic and pharmacodynamic trials will be highly valuable in evaluating the clinical significance of this interaction and determining whether dosage modifications are indicated.

Indexed as

Drug InteractionsAdultAnti-HIV AgentsAntimalarialsAntiretroviral Therapy, Highly ActiveFemaleHIV InfectionsHumansMalariaMaleUgandaAnti-HIV AgentsAntimalarials

Identifiers

PMID22316571
PMCPMC3324422
OpenAlexW2138474554

What OpenQuestion holds

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LicenceCC BY-NC
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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.