Publication: Significant pharmacokinetic interactions between artemether/lumefantrine and efavirenz or nevirapine in HIV-infected Ugandan adults
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Issued Date
2012-09-01
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ISSN
14602091
03057453
03057453
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2-s2.0-84865350852
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Mahidol University
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SCOPUS
Bibliographic Citation
Journal of Antimicrobial Chemotherapy. Vol.67, No.9 (2012), 2213-2221
Suggested Citation
Pauline Byakika-Kibwika, Mohammed Lamorde, Jonathan Mayito, Lillian Nabukeera, Rhoda Namakula, Harriet Mayanja-Kizza, Elly Katabira, Muhammad Ntale, Nadine Pakker, Mairin Ryan, Warunee Hanpithakpong, Joel Tarning, Niklas Lindegardh, Peter J. De vries, Saye Khoo, David Back, Concepta Merry Significant pharmacokinetic interactions between artemether/lumefantrine and efavirenz or nevirapine in HIV-infected Ugandan adults. Journal of Antimicrobial Chemotherapy. Vol.67, No.9 (2012), 2213-2221. doi:10.1093/jac/dks207 Retrieved from: https://repository.li.mahidol.ac.th/handle/123456789/14680
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Title
Significant pharmacokinetic interactions between artemether/lumefantrine and efavirenz or nevirapine in HIV-infected Ugandan adults
Abstract
Objectives: Co-administration of artemether/lumefantrine with antiretroviral therapy has potential for pharmacokinetic drug interactions. We investigated drug-drug interactions between artemether/lumefantrine and efavirenz or nevirapine. Methods: We performed a cross-over study in which HIV-infected adults received standard six-dose artemether/lumefantrine 80/480 mg before and at efavirenz or nevirapine steady state. Artemether, dihydroartemisinin, lumefantrine, efavirenz and nevirapine plasma concentrations were measured and compared. Results: Efavirenz significantly reduced artemether maximum concentration (C max ) and plasma AUC (median 29 versus 12 ng/mL, P < 0.01, and 119 versus 25 ng · h/mL, P < 0.01), dihydroartemisinin C max and AUC (median 120 versus 26 ng/mL, P < 0.01, and 341 versus 84 ng · h/mL, P < 0.01), and lumefantrine C max and AUC (median 8737 versus 6331 ng/mL, P = 0.03, and 280 370 versus 124 381 ng · h/mL, P < 0.01). Nevirapine significantly reduced artemether C max and AUC (median 28 versus 11 ng/mL, P < 0.01, and 123 versus 34 ng · h/mL, P < 0.01) and dihydroartemisinin C max and AUC (median 107 versus 59 ng/mL, P < 0.01, and 364 versus 228 ng · h/mL, P < 0.01). Lumefantrine C max and AUC were non-significantly reduced by nevirapine. Artemether/lumefantrine reduced nevirapine C max and AUC (median 8620 versus 4958 ng/mL, P < 0.01, and 66 329 versus 35 728 ng · h/mL, P < 0.01), but did not affect efavirenz exposure. Conclusions: Co-administration of artemether/lumefantrine with efavirenz or nevirapine resulted in a reduction in artemether, dihydroartemisinin, lumefantrine and nevirapine exposure. These drug interactions may increase the risk of malaria treatment failure and development of resistance to artemether/lumefantrine and nevirapine. Clinical data from population pharmacokinetic and pharmacodynamic trials evaluating the impact of these drug interactions are urgently needed. © The Author 2012. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved.