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Artemether-lumefant...
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Höglund, Richard,1984Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi, sektionen för farmakologi,Institute of Neuroscience and Physiology, Department of Pharmacology
(author)
Artemether-lumefantrine coadministration with antiretrovirals; population pharmacokinetics and dosing implications
- Article/chapterEnglish2015
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LIBRIS-ID:oai:gup.ub.gu.se/206625
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https://gup.ub.gu.se/publication/206625URI
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https://doi.org/10.1111/bcp.12529DOI
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Subject category:ref swepub-contenttype
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Subject category:art swepub-publicationtype
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AimDrug-drug interactions between antimalarial and antiretroviral drugs may influence antimalarial treatment outcomes. The aim of this study was to investigate the potential drug-drug interactions between the anti-malarial drugs; lumefantrine, artemether and their respective metabolites desbutyl-lumefantrine and dihydroartemisinin, and the HIV-drugs efavirenz, nevirapine and lopinavir/ritonavir.Method Data from two clinical studies, investigating the influence of the HIV-drugs efavirenz, nevirapine and lopinavir/ritonavir on the pharmacokinetics of the antimalarial drugs lumefantrine, artemether and their respective metabolites, in HIV infected patients were pooled and analysed using a nonlinear mixed-effects modelling approach.ResultsEfavirenz and nevirapine significantly decreased the terminal exposure to lumefantrine (decrease of 69.9% and 25.2%, respectively) while lopinavir/ritonavir substantially increased the exposure (increase of 439%). All antiretroviral drugs decreased the total exposure to dihydroartemisinin (decrease of 71.7%, 41.3% and 59.7% for efavirenz, nevirapine and ritonavir/lopinavir, respectively). Simulations suggest that a substantially increased artemether-lumefantrine dose is required to achieve equivalent exposures when co-administered with efavirenz (250% increase) and nevirapine (75% increase). When co-administered with lopinavir/ritonavir it is unclear if the increased lumefantrine exposure compensates adequately for the reduced dihydroartemisinin exposure and thus whether dose adjustment is required.Conclusion There are substantial drug interactions between artemether-lumefantrine and efavirenz, nevirapine and ritonavir/lopinavir. Given the readily saturable absorption of lumefantrine, the dose adjustments predicted to be necessary will need to be evaluated prospectively in malaria-HIV coinfected patients.
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Byakika‐Kibwika, Pauline
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Lamorde, Mohammed
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Merry, Concepta
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Ashton, Michael,1955Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi, sektionen för farmakologi,Institute of Neuroscience and Physiology, Department of Pharmacology(Swepub:gu)xashmi
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Day, Nicholas Philip John
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White, Nicholas J
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Abelö, AngelaGothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi, sektionen för farmakologi,Institute of Neuroscience and Physiology, Department of Pharmacology
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Tärning, Joel,1977
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Göteborgs universitetInstitutionen för neurovetenskap och fysiologi, sektionen för farmakologi
(creator_code:org_t)
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In:British Journal of Clinical Pharmacology: Wiley79:4, s. 636-6490306-52511365-2125
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