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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
medicine
Lopinavir/ritonavir significantly influences pharmacokinetic exposure of artemether/lumefantrine in HIV-infected Ugandan adults
Journal of Antimicrobial Chemotherapy, Volume 67, No. 5, Article dkr596, Year 2012
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Description
Background: Treatment of HIV/malaria-coinfected patients with antiretroviral therapy (ART) and artemisinin-based 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 (C max) and area under the concentration-time curve (AUC) [median (range): 112 (20-362) versus 56 (17-236) ng/mL, P = 0.03; and 264 (92-1129) versus 151 (38-606) ng · h/mL, P < 0.01]. Dihydroartemisinin C max and AUC were not affected [66 (10-111) versus 73 (31-224) ng/mL, P = 0.55; and 213 (68-343) versus 175 (118-262) ng · h/mL P = 0.27]. Lumefantrine C max and AUC increased during co-administration [2532 (1071-5957) versus 7097 (2396-9462) ng/mL, P < 0.01; and 41 119 (12 850-125 200) versus 199 678 (71 205-251 015) 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. © The Author 2012. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy.
Authors & Co-Authors
Byakika-Kibwika, Pauline
Uganda, Kampala
Makerere University
Ireland, Dublin
Trinity College Dublin
Uganda, Kampala
Infectious Diseases Network for Treatment and Research in Africa
Lamorde, Mohammed
Uganda, Kampala
Makerere University
Ireland, Dublin
Trinity College Dublin
Okaba-Kayom, Violet
Uganda, Kampala
Makerere University
Mayanja-Kizza, Harriet
Uganda, Kampala
Makerere University
Uganda, Kampala
Infectious Diseases Network for Treatment and Research in Africa
Katabira, Elly Tebasoboke
Uganda, Kampala
Makerere University
Uganda, Kampala
Infectious Diseases Network for Treatment and Research in Africa
Hanpithakpong, Warunee
Thailand, Nakhon Pathom
Mahidol University
Pakker, Nadine G.
Uganda, Kampala
Infectious Diseases Network for Treatment and Research in Africa
Dorlo, Thomas P.C.
Netherlands, Amsterdam
The Netherlands Cancer Institute
Netherlands, Amsterdam
Amsterdam Umc - University of Amsterdam
Tarning, Joel
Thailand, Nakhon Pathom
Mahidol University
United Kingdom, Oxford
Nuffield Department of Medicine
Lindegårdh, Niklas
Thailand, Nakhon Pathom
Mahidol University
United Kingdom, Oxford
Nuffield Department of Medicine
de Vries, Peter J.
Netherlands, Amsterdam
Amsterdam Umc - University of Amsterdam
Back, David J.
United Kingdom, Liverpool
University of Liverpool
Khoo, Saye Hock
United Kingdom, Liverpool
University of Liverpool
Merry, Concepta
Uganda, Kampala
Makerere University
Ireland, Dublin
Trinity College Dublin
Uganda, Kampala
Infectious Diseases Network for Treatment and Research in Africa
Statistics
Citations: 50
Authors: 14
Affiliations: 8
Identifiers
Doi:
10.1093/jac/dkr596
ISSN:
03057453
e-ISSN:
14602091
Research Areas
Cancer
Infectious Diseases
Noncommunicable Diseases
Study Design
Cross Sectional Study