Artemether-lumefantrine coadministration with antiretrovirals; population pharmacokinetics and dosing implications.
AIM: Drug-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-l...
| Main Authors: | , , , , , , , , , |
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| Format: | Journal article |
| Language: | English |
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2014
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| _version_ | 1826292534487285760 |
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| author | Hoglund, R Byakika-Kibwika, P Lamorde, M Merry, C Ashton, M Hanpithakpong, W Day, N White, N Abelö, A Tarning, J |
| author_facet | Hoglund, R Byakika-Kibwika, P Lamorde, M Merry, C Ashton, M Hanpithakpong, W Day, N White, N Abelö, A Tarning, J |
| author_sort | Hoglund, R |
| collection | OXFORD |
| description | AIM: Drug-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. RESULTS: Efavirenz 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. |
| first_indexed | 2024-03-07T03:16:11Z |
| format | Journal article |
| id | oxford-uuid:b5de0ae6-537e-4437-94fd-888642eeaaea |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T03:16:11Z |
| publishDate | 2014 |
| record_format | dspace |
| spelling | oxford-uuid:b5de0ae6-537e-4437-94fd-888642eeaaea2022-03-27T04:36:47ZArtemether-lumefantrine coadministration with antiretrovirals; population pharmacokinetics and dosing implications.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:b5de0ae6-537e-4437-94fd-888642eeaaeaEnglishSymplectic Elements at Oxford2014Hoglund, RByakika-Kibwika, PLamorde, MMerry, CAshton, MHanpithakpong, WDay, NWhite, NAbelö, ATarning, JAIM: Drug-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. RESULTS: Efavirenz 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. |
| spellingShingle | Hoglund, R Byakika-Kibwika, P Lamorde, M Merry, C Ashton, M Hanpithakpong, W Day, N White, N Abelö, A Tarning, J Artemether-lumefantrine coadministration with antiretrovirals; population pharmacokinetics and dosing implications. |
| title | Artemether-lumefantrine coadministration with antiretrovirals; population pharmacokinetics and dosing implications. |
| title_full | Artemether-lumefantrine coadministration with antiretrovirals; population pharmacokinetics and dosing implications. |
| title_fullStr | Artemether-lumefantrine coadministration with antiretrovirals; population pharmacokinetics and dosing implications. |
| title_full_unstemmed | Artemether-lumefantrine coadministration with antiretrovirals; population pharmacokinetics and dosing implications. |
| title_short | Artemether-lumefantrine coadministration with antiretrovirals; population pharmacokinetics and dosing implications. |
| title_sort | artemether lumefantrine coadministration with antiretrovirals population pharmacokinetics and dosing implications |
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