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Please use this identifier to cite or link to this item: http://repository.li.mahidol.ac.th/dspace/handle/123456789/27996
Title: Lopinavir/ritonavir affects pharmacokinetic exposure of artemether/lumefantrine in HIV-uninfected healthy volunteers
Authors: Polina German
Sunil Parikh
Jody Lawrence
Grant Dorsey
Philip J. Rosenthal
Diane Havlir
Edwin Charlebois
Warunee Hanpithakpong
Niklas Lindegardh
Francesca T. Aweeka
University of California, San Francisco
UCSF School of Medicine
Mahidol University
Nuffield Department of Clinical Medicine
Keywords: Medicine
Issue Date: 1-Aug-2009
Citation: Journal of Acquired Immune Deficiency Syndromes. Vol.51, No.4 (2009), 424-429
Abstract: Objectives: Antimalarial combination therapy is used in persons with HIV infection in the absence of data on drug interactions. The objective of this study was to investigate the pharmacokinetics (PK) of antimalarial combination artemether/lumefantrine (AL) when administered with the protease inhibitor combination lopinavir/ritonavir (LPV/r) in HIV-uninfected healthy volunteers to determine if important drug interactions exist between these agents. Design: Open-label study in healthy HIV-seronegative adults. Methods: Participants received standard 6-dose treatment courses of AL 80/480 mg twice daily on days 1-4 and 28-31. LPV/r 400/100 mg twice daily was administered on days 16-41 after a 2-week washout period. Plasma concentrations of AL, dihydroartemisinin (DHA, artemether metabolite), lopinavir, and ritonavir were measured. Results: PK of lumefantrine was influenced by LPV/r resulting in 2- to 3-fold increases in area under the curve (AUC) (AUC0-264: 413 versus 931 h·μ g·mL-1; AUC0-inf: 456 versus 1073 h·μg·mL-1). For artemether, trends toward Cmaxand AUC decreases (Cmax14.3 versus 11.2 ng/mL and 42.7-62.0 versus 25.9-40.5 h·ng·mL-1for AUC) were noted during coadministration. For DHA, decreases in Cmax(58.8 versus 37.3 ng/mL) and AUC (190-198 versus 104-109 h·ng·mL-1) were observed during coadministration without changes in DHA:artemether AUC ratios. AL did not affect LPV/r PK. Conclusions: Coadministration of artmether/lumefantrine and LPV/r can be carried out for patients coinfected with malaria and HIV. Formal safety analysis of concomitant therapy should be addressed by future studies among individuals living in malaria-endemic regions. Copyright © 2009 by Lippincott Williams & Wilkins.
URI: https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=68049121902&origin=inward
http://repository.li.mahidol.ac.th/dspace/handle/123456789/27996
ISSN: 15254135
Appears in Collections:Scopus 2006-2010

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