Artemether-lumefantrine is often coadministered with
efavirenz-based antiretroviral
therapy for
malaria treatment in HIV-infected women during pregnancy. Previous studies showed changes in
lumefantrine pharmacokinetics due to interaction with
efavirenz in nonpregnant adults. The influence of pregnancy on this interaction has not been reported. This pharmacokinetic study involved 35 pregnant and 34 nonpregnant HIV-
malaria-coinfected women receiving
efavirenz-based antiretroviral
therapy and was conducted in four health facilities in Nigeria. Participants received a 3-day standard regimen of
artemether-lumefantrine for
malaria treatment, and intensive pharmacokinetic sampling was conducted from 0.5 to 96 h after the last dose. Plasma
efavirenz,
lumefantrine, and desbutyl-
lumefantrine were quantified using validated assays, and pharmacokinetic parameters were derived using noncompartmental analysis. The median middose plasma concentrations of
efavirenz were significantly lower in pregnant women (n = 32) than in nonpregnant women (n = 32) at 1,820 ng/ml (interquartile range, 1,300 to 2,610 ng/ml) versus 2,760 ng/ml (interquartile range, 2,020 to 5,640 ng/ml), respectively (P = 0.006). The
lumefantrine area under the concentration-time curve from 0 to 96 h was significantly higher in pregnant women (n = 27) at 155,832 ng · h/ml (interquartile range, 102,400 to 214,011 ng · h/ml) than nonpregnant women at 90,594 ng · h/ml (interquartile range, 58,869 to 149,775 ng · h/ml) (P = 0.03). A similar trend was observed for the
lumefantrine concentration at 12 h after the last dose of
lumefantrine, which was 2,870 ng/ml (interquartile range, 2,180 to 4,880 ng/ml) versus 2,080 ng/ml (interquartile range, 1,190 to 2,970 ng/ml) in pregnant and nonpregnant women, respectively (P = 0.02). The
lumefantrine-to-desbutyl-
lumefantrine ratio also tended to be lower in pregnant women than in nonpregnant women (P = 0.076). Overall, pregnancy tempered the extent of
efavirenz-
lumefantrine interactions, resulting in increased
lumefantrine exposure. However, any consideration of dosage adjustment for
artemether-lumefantrine to enhance exposure in this population needs to be based on data from a prospective study with safety and efficacy endpoints.