mirage

Lopinavir/ritonavir significantly influences pharmacokinetic exposure of artemether/lumefantrine in HIV-infected Ugandan adults

Mak IR/Manakin Repository

Show simple item record

dc.contributor.author Byakika-Kibwika, Pauline
dc.contributor.author Lamorde, Mohammed
dc.contributor.author Okaba-Kayom, Violet
dc.contributor.author Mayanja-Kizza, Harriet
dc.contributor.author Katabira, Elly
dc.contributor.author Hanpithakpong, Warunee
dc.contributor.author Pakker, Nadine
dc.contributor.author Dorlo, Thomas P. C.
dc.contributor.author Tarning, Joel
dc.contributor.author Lindegardh, Niklas
dc.contributor.author de Vries, Peter J.
dc.contributor.author Back, David
dc.contributor.author Khoo, Saye
dc.contributor.author Merry, Concepta
dc.date.accessioned 2012-11-23T06:35:58Z
dc.date.available 2012-11-23T06:35:58Z
dc.date.issued 2012-02-08
dc.identifier.citation Byakika-Kibwika, P. et al. (2012). Lopinavir/ritonavir significantly influences pharmacokinetic exposure of artemether/lumefantrine in HIV-infected Ugandan adults. Journal of Antimicrobial Chemotherapy, 67: 1217-1223 en_US
dc.identifier.issn 0305-7453
dc.identifier.uri http://hdl.handle.net/10570/896
dc.description.abstract Background: Treatment of HIV/malaria-coinfected patients with antiretroviral therapy (ART) and artemisininbased combination therapy has potential for drug interactions. We investigated the pharmacokinetics of artemether, dihydroartemisinin and lumefantrine after administration of a single dose of 80/480 mg of artemether/ lumefantrine to HIV-infected adults, taken with and without lopinavir/ritonavir. Methods: A two-arm parallel study of 13 HIV-infected ART-naive adults and 16 HIV-infected adults stable on 400/100 mg of lopinavir/ritonavir plus two nucleoside reverse transcriptase inhibitors (ClinicalTrials.gov, NCT 00619944). Each participant received a single dose of 80/480 mg of artemether/lumefantrine under continuous cardiac function monitoring. Plasma concentrations of artemether, dihydroartemisinin and lumefantrine were measured. Results: Co-administration of artemether/lumefantrine with lopinavir/ritonavir significantly reduced artemether maximum concentration (Cmax) and area under the concentration–time curve (AUC) [median (range): 112 (20–362) versus 56 (17–236) ng/mL, P¼0.03; and 264 (92–1129) versus 151 (38–606) ng.h/mL, P,0.01]. Dihydroartemisinin Cmax and AUC were not affected [66 (10–111) versus 73 (31–224) ng/mL, P¼0.55; and 213 (68–343) versus 175 (118–262) ng.h/mL P¼0.27]. Lumefantrine Cmax and AUC increased during co-administration [2532 (1071–5957) versus 7097 (2396–9462) ng/mL, P,0.01; and 41119 (12850–125200) versus 199678 (71205–251015) ng.h/mL, P,0.01]. Conclusions: Co-administration of artemether/lumefantrine with lopinavir/ritonavir significantly increases lumefantrine exposure, but decreases artemether exposure. Population pharmacokinetic and pharmacodynamic trials will be highly valuable in evaluating the clinical significance of this interaction and determining whether dosage modifications are indicated. en_US
dc.description.sponsorship Support for this study was provided by a Monument Fund grant to the University of Liverpool, UK. Additional support was provided by the Infectious Diseases Network for Treatment and Research in Africa and the HIV Research Trust. W. H., J. T. and N. L. are part of the Wellcome Trust-Mahidol University-Oxford Tropical Medicine Research Programme (077166/Z/05/Z) supported by the Wellcome Trust of Great Britain. en_US
dc.language.iso en en_US
dc.publisher Journal of Antimicrobial Chemotherapy en_US
dc.subject Antiretrovirals en_US
dc.subject Antimalarials en_US
dc.subject Drug interactions en_US
dc.title Lopinavir/ritonavir significantly influences pharmacokinetic exposure of artemether/lumefantrine in HIV-infected Ugandan adults en_US
dc.type Journal article, peer reviewed en_US


Files in this item

This item appears in the following Collection(s)

Show simple item record