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• W1972128519 endingPage "151" @default.
• W1972128519 startingPage "141" @default.
• W1972128519 abstract "Forty-two healthy subjects were randomized in a parallel three-group design trial to investigate potential electrocardiographic and pharmacokinetic interactions between the new antimalarial co-artemether, a combination of artemether and lumefantrine (both of which are predominantly metabolized through CYP3A4), and mefloquine, another antimalarial described as a substrate (and possible inhibitor) of CYP3A4. Subjects were assigned to one of the three possible treatment groups (i.e., co-artemether alone or mefloquine alone or the combination of both). The dosage was 1000 mg mefloquine (divided into three doses over 12 h) followed 12 h later by six applications of co-artemether (40 mg artemether+480 mg lumefantrine each) over 60 h. The study medications were generally well tolerated after all treatments. Concomitant administration with mefloquine caused statistically significant lower (around 30-40%) plasma concentrations of lumefantrine than when co-artemether was administered alone. Even if important, this decrease in lumefantrine exposure was considered unlikely to impact clinical efficacy given the wide therapeutic index of co-artemether and the usual high variability in lumefantrine plasma levels, mostly and more importantly influenced by food intake. However, patients should be encouraged to eat at dosing times to compensate for this decreased bioavailability. The pharmacokinetics of artemether, DHA or mefloquine were not affected. Artemether concentrations significantly decreased over doses, independently of mefloquine co-administration, while DHA concentrations slightly (not significantly) increased. Therefore, no clinically relevant risks due to pharmacokinetic drug-drug interaction are expected at the enzymatic level following co-administration of co-artemether with CYP3A4 substrates with similar affinity to that of mefloquine." @default.
• W1972128519 created "2016-06-24" @default.
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• W1972128519 date "2000-04-01" @default.
• W1972128519 modified "2023-10-16" @default.
• W1972128519 title "Pharmacokinetic interaction trial between co-artemether and mefloquine" @default.
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• W1972128519 doi "https://doi.org/10.1016/s0928-0987(00)00060-9" @default.
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