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Artemether-lumefant...
Artemether-lumefantrine coadministration with antiretrovirals; population pharmacokinetics and dosing implications
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- Höglund, Richard, 1984 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi, sektionen för farmakologi,Institute of Neuroscience and Physiology, Department of Pharmacology
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Byakika‐Kibwika, Pauline (author)
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Lamorde, Mohammed (author)
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Merry, Concepta (author)
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- Ashton, Michael, 1955 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi, sektionen för farmakologi,Institute of Neuroscience and Physiology, Department of Pharmacology
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Day, Nicholas Philip John (author)
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White, Nicholas J (author)
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- Abelö, Angela (author)
- Gothenburg 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 (author)
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(creator_code:org_t)
- 2015-03-23
- 2015
- English.
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In: British Journal of Clinical Pharmacology. - : Wiley. - 0306-5251 .- 1365-2125. ; 79:4
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Abstract
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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.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Farmaceutiska vetenskaper (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Pharmaceutical Sciences (hsv//eng)
Publication and Content Type
- ref (subject category)
- art (subject category)
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Höglund, Richard ...
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Byakika‐Kibwika, ...
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Lamorde, Mohamme ...
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Merry, Concepta
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Ashton, Michael, ...
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Day, Nicholas Ph ...
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White, Nicholas ...
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Abelö, Angela
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Tärning, Joel, 1 ...
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- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Basic Medicine
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and Pharmaceutical S ...
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British Journal ...
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University of Gothenburg