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dc.contributor.authorByakika-Kibwika, Pauline
dc.contributor.authorLamorde, Mohammed
dc.contributor.authorMayito, Jonathan
dc.contributor.authorNabukeera, Lillian
dc.contributor.authorNamakula, Rhoda
dc.contributor.authorMayanja-Kizza, Harriet
dc.contributor.authorKatabira, Elly
dc.contributor.authorNtale, Muhammad
dc.contributor.authorPakker, Nadine
dc.contributor.authorRyan, Mairin
dc.contributor.authorHanpithakpong, Warunee
dc.contributor.authorTarning, Joel
dc.contributor.authorLindegardh, Niklas
dc.contributor.authorKhoo, Saye
dc.contributor.authorBack, David
dc.contributor.authorMerry, Concepta
dc.date.accessioned2013-01-03T07:52:54Z
dc.date.available2013-01-03T07:52:54Z
dc.date.issued2012
dc.identifier.citationByakika-Kibwika, P., Lamorde, M., Mayito, J., Nabukeera, L., Namakula, R., Mayanja-Kizza, H., Katabira, E., Ntale, M., Hanpithakpong, W., Obua, C., Pakker, N., Ryan, M., Lindegardh, N., Tarning, J., de Vries, P.J., Khoo, S., Back, D., Merry, C. (2012). Significant pharmacokinetic interactions between artemether/lumefantrine and efavirenz or nevirapine in HIV-infected Ugandan adults. Journal of Antimicrobial Chemotherapy, 67(9)en_US
dc.identifier.issn1460-2091
dc.identifier.uridoi:10.1093/jac/dks207
dc.identifier.urihttp://hdl.handle.net/10570/943
dc.description.abstractObjectives: 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 (Cmax) and plasma AUC (median 29 versus 12 ng/mL, P,0.01, and 119 versus 25 ng.h/mL, P,0.01), dihydroartemisinin Cmax and AUC (median 120 versus 26 ng/mL, P,0.01, and 341 versus 84 ng.h/mL, P,0.01), and lumefantrine Cmax and AUC (median 8737 versus 6331 ng/mL, P¼0.03, and 280370 versus 124381 ng.h/mL, P,0.01). Nevirapine significantly reduced artemether Cmax and AUC (median 28 versus 11 ng/mL, P,0.01, and 123 versus 34 ng.h/mL, P,0.01) and dihydroartemisinin Cmax and AUC (median 107 versus 59 ng/mL, P,0.01, and 364 versus 228 ng.h/mL, P,0.01). Lumefantrine Cmax and AUC were non-significantly reduced by nevirapine. Artemether/lumefantrine reduced nevirapine Cmax and AUC (median 8620 versus 4958 ng/mL, P,0.01, and 66329 versus 35728 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 neededen_US
dc.description.sponsorshipThis work was supported by the Health Research Board, Ireland, the Infectious Diseases Network for Treatment and Research in Africa and the HIV Research Trust and the Wellcome Trust of Great Britain.en_US
dc.language.isoenen_US
dc.publisherOxford University Pressen_US
dc.subjectAntimalarialsen_US
dc.subjectAntiretroviralsen_US
dc.subjectMalariaen_US
dc.subjectHIV/AIDSen_US
dc.titleSignificant pharmacokinetic interactions between artemether/lumefantrine and efavirenz or nevirapine in HIV-infected Ugandan adultsen_US
dc.typeJournal article, peer revieweden_US


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