Lopinavir/ritonavir affects pharmacokinetic exposure of artemether/lumefantrine in HIV-uninfected healthy volunteers.
OBJECTIVE
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.


METHODS
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.
German
Polina
P
Department of Clinical Pharmacy, Drug Research, University of California, School of Medicine, San Francisco, CA 94143-0622, USA.
Parikh
Sunil
S
Lawrence
Jody
J
Dorsey
Grant
G
Rosenthal
Philip J
PJ
Havlir
Diane
D
Charlebois
Edwin
E
Hanpithakpong
Warunee
W
Lindegardh
Niklas
N
Aweeka
Francesca T
FT
D000328:Adult; D000962:Antimalarials / Q000493:pharmacokinetics*; D019540:Area Under Curve; D000077549:Artemether; D037621:Artemisinins / Q000493:pharmacokinetics*; D051544:Cytochrome P-450 CYP3A / Q000502:physiology; D004347:Drug Interactions; D004983:Ethanolamines / Q000493:pharmacokinetics*; D005260:Female; D005449:Fluorenes / Q000493:pharmacokinetics*; D017320:HIV Protease Inhibitors / Q000494:pharmacology*; D006801:Humans; D061466:Lopinavir; D000078102:Lumefantrine; D008297:Male; D008875:Middle Aged; D011744:Pyrimidinones / Q000494:pharmacology*; D019438:Ritonavir / Q000494:pharmacology*
D000962:Antimalarials; D037621:Artemisinins; D004983:Ethanolamines; D005449:Fluorenes; D017320:HIV Protease Inhibitors; D011744:Pyrimidinones; D061466:Lopinavir; D000077549:Artemether; D051544:Cytochrome P-450 CYP3A; C510163:CYP3A4 protein, human; D000078102:Lumefantrine; D019438:Ritonavir