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An individual participant data population pharmacokinetic meta-analysis of drug-drug interactions between lumefantrine and commonly used antiretroviral treatment

Title: An individual participant data population pharmacokinetic meta-analysis of drug-drug interactions between lumefantrine and commonly used antiretroviral treatment
Authors: Francis, J; Barnes, KI; Workman, L; Kredo, T; Vestergaard, LS; Hoglund, RM; Byakika-Kibwika, P; Lamorde, M; Walimbwa, SI; Chijioke-Nwauche, I; Sutherland, CJ; Merry, C; Scarsi, KK; Nyagonde, N; Lemnge, MM; Khoo, SH; Bygbjerg, IC; Parikh, S; Aweeka, FT; Tarning, J; Denti, P
Publisher Information: American Society for Microbiology
Publication Year: 2020
Collection: Oxford University Research Archive (ORA)
Description: Treating malaria in HIV-coinfected individuals should consider potential drug-drug interactions. Artemether-lumefantrine is the most widely recommended treatment for uncomplicated malaria globally. Lumefantrine is metabolized by CYP3A4, an enzyme that commonly used antiretrovirals often induce or inhibit. A population pharmacokinetic meta-analysis was conducted using individual participant data from 10 studies with 6,100 lumefantrine concentrations from 793 nonpregnant adult participants (41% HIV-malaria-coinfected, 36% malaria-infected, 20% HIV-infected, and 3% healthy volunteers). Lumefantrine exposure increased 3.4-fold with coadministration of lopinavir-ritonavir-based antiretroviral therapy (ART), while it decreased by 47% with efavirenz-based ART and by 59% in the patients with rifampin-based antituberculosis treatment. Nevirapine- or dolutegravir-based ART and malaria or HIV infection were not associated with significant effects. Monte Carlo simulations showed that those on concomitant efavirenz or rifampin have 49% and 80% probability of day 7 concentrations
Document Type: article in journal/newspaper
Language: English
DOI: 10.1128/aac.02394-19
Availability: https://doi.org/10.1128/aac.02394-19; https://ora.ox.ac.uk/objects/uuid:1f18baa0-92fe-4c07-aff6-be5cebd6a961
Rights: info:eu-repo/semantics/openAccess ; CC Attribution (CC BY)
Accession Number: edsbas.99430AE7
Database: BASE