Abstract | OBJECTIVES: 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.microg.mL; AUC0-inf: 456 versus 1073 h.microg.mL). For artemether, trends toward Cmax and AUC decreases (Cmax 14.3 versus 11.2 ng/mL and 42.7-62.0 versus 25.9-40.5 h.ng.mL for 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) 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.
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Authors | Polina German, Sunil Parikh, Jody Lawrence, Grant Dorsey, Philip J Rosenthal, Diane Havlir, Edwin Charlebois, Warunee Hanpithakpong, Niklas Lindegardh, Francesca T Aweeka |
Journal | Journal of acquired immune deficiency syndromes (1999)
(J Acquir Immune Defic Syndr)
Vol. 51
Issue 4
Pg. 424-9
(Aug 01 2009)
ISSN: 1525-4135 [Print] United States |
PMID | 19506482
(Publication Type: Journal Article)
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Chemical References |
- Antimalarials
- Artemisinins
- Ethanolamines
- Fluorenes
- HIV Protease Inhibitors
- Pyrimidinones
- Lopinavir
- Artemether
- Cytochrome P-450 CYP3A
- CYP3A4 protein, human
- Lumefantrine
- Ritonavir
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Topics |
- Adult
- Antimalarials
(pharmacokinetics)
- Area Under Curve
- Artemether
- Artemisinins
(pharmacokinetics)
- Cytochrome P-450 CYP3A
(physiology)
- Drug Interactions
- Ethanolamines
(pharmacokinetics)
- Female
- Fluorenes
(pharmacokinetics)
- HIV Protease Inhibitors
(pharmacology)
- Humans
- Lopinavir
- Lumefantrine
- Male
- Middle Aged
- Pyrimidinones
(pharmacology)
- Ritonavir
(pharmacology)
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