Background: Artemether-lumefantrine (CoartemW; AL) is a standard of care for malaria treatment as an oral\r\nsix-dose regimen, given twice daily over three days with one to four tablets (20/120 mg) per dose, depending on\r\npatient body weight. In order to reduce the pill burden at each dose and potentially enhance compliance, two\r\nnovel fixed-dose tablet formulations (80/480 mg and 60/360 mg) have been developed and tested in this study for\r\nbioequivalence with their respective number of standard tablets.\r\nMethods: A randomized, open-label, two-period, single-dose, within formulation crossover bioequivalence study\r\ncomparing artemether and lumefantrine exposure between the novel 80/480 mg tablet and four standard tablets,\r\nand the novel 60/360 mg tablet and three standard tablets, was conducted in 120 healthy subjects under fed\r\nconditions. Artemether, dihydroartemisinin, and lumefantrine were measured in plasma by HPLC/UPLC-MS/MS.\r\nPharmacokinetic (PK) parameters were determined by non-compartmental analyses.\r\nResults: Adjusted geometric mean AUClast for artemether were 345 and 364 ng�·h/mL (geometric mean ratio (GMR)\r\n0.95; 90% CI 0.89-1.01) and for lumefantrine were 219 and 218 �µg�·h/mL (GMR 1.00; 90% CI 0.93-1.08) for 80/480 mg\r\ntablet versus four standard tablets, respectively. Corresponding Cmax for artemether were 96.8 and 99.7 ng/mL\r\n(GMR 0.97; 90% CI 0.89-1.06) and for lumefantrine were 8.42 and 8.71 �µg/mL (GMR 0.97; 90% CI 0.89-1.05). For the\r\n60/360 mg tablet versus three standard tablets, adjusted geometric mean AUClast for artemether were 235 and\r\n231 ng�·h/mL (GMR 1.02; 90% CI 0.94-1.10), and for lumefantrine were 160 and 180 �µg�·h/mL (GMR 0.89; 90%\r\nCI 0.83-0.96), respectively. Corresponding Cmax for artemether were 75.5 and 71.5 ng/mL (GMR 1.06; 90%\r\nCI 0.95-1.18), and for lumefantrine were 6.64 and 7.61 �µg/mL (GMR 0.87; 90% CI 0.81-0.94), respectively. GMR for\r\nCmax and AUClast for artemether and lumefantrine for all primary comparisons were within the bioequivalence\r\nacceptance criteria (0.80-1.25). In addition, secondary PK parameters also met bioequivalence criterion.\r\nConclusion: Both of the novel artemether-lumefantrine tablet formulations evaluated are bioequivalent to their\r\nrespective standard CoartemW tablet doses. These novel formulations are easy to administer and may improve\r\nadherence in the treatment of uncomplicated malaria caused by Plasmodium falciparum.
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