Bioavailability of lumefantrine is significantly enhanced with a novel formulation approach: A randomized, open-label pharmacokinetic study in healthy volunteers [PublishAheadOfPrint]

The artemether-lumefantrine combination requires food intake for optimal absorption of lumefantrine. In an attempt to enhance bioavailability of lumefantrine, new solid dispersion formulations (SDF) were developed, and the pharmacokinetics of two SDF variants were assessed in a randomized, open-label, sequential two-part study in healthy volunteers. In Part 1, relative bioavailability of the two SDF variants was compared with the conventional formulation after administration of a single dose of 480 mg under fasted conditions in three parallel cohorts. In Part 2, pharmacokinetics of lumefantrine from both SDF variants was evaluated after a single dose of 480 mg under fed conditions and a single dose of 960 mg under fasted conditions.

The bioavailability of lumefantrine from SDF variant-1 and variant-2 increased up to ~48-fold and ~24-fold, respectively, relative to the conventional formulation. Both variants demonstrated positive food effect and less than proportional increase in exposure between 480 mg and 960 mg doses.

Most AEs were mild to moderate in severity and not suspected to be related to the study drug. All five drug-related AEs occurred in subjects taking SDF variant-2. No clinically-significant treatment-emergent changes were noted in vital signs, ECG, or laboratory blood assessments.

The Solid Dispersion Formulation enhances lumefantrine bioavailability to a significant extent and SDF variant-1 is superior to SDF variant-2.

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