Lopinavir/r affects PK exposure of some antimalarial drugs

This study investigated the pharmacokinetics (PK) of the antimalarial combination artemether/lumefantrine when administered with lopinavir/ritonavir (LPV/r) in HIV-uninfected healthy volunteers. Ten participants completed having received standard 6-day treatment courses of artemether/lumefantrine (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 lumefantrine, artemether, dihydroartemisinin (DHA, artemether metabolite), lopinavir, and ritonavir were measured.

The PK of lumefantrine was influenced by LPV/r resulting in 2-3-fold increases in AUC (AUC0-264, 413 versus 931 h.µg.mL; AUC0-inf, 456 versus 1073 h.µg.mL). For artemether, a trend towards an AUC decrease (42.7-62.0 versus 25.9-40.5 was noted during coadministration. For DHA, a decrease in AUC (190-198 versus 104-109 was observed during coadministration without changes in DHA:artemether AUC ratios. The pharmacokinetics of lopinavir or ritonavir were not affected by artemether/lumefantrine.

These are important data for a complex interaction. Overall the authors conclude that coadministration of artemether/lumefantrine and LPV/r can be carried out for patients coinfected with malaria and HIV. Indeed, they suggest that the increase in lumefantrine AUC may be beneficial in the treatment of malaria. However, formal safety analysis of concomitant therapy should be addressed by future studies among individuals living in malaria-endemic regions.

Source: (July 2009)


German P et al. ritonavir affects pharmacokinetic exposure of artemether/lumefantrine in HIV-uninfected healthy volunteers. J Acquir Immune Defic Syndr. 2009, epub ahead of print.

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