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Bioavailability of lumefantrine is significantly enhanced with a novel formulation approach, an outcome from a randomized, Open-label pharmacokinetic study in healthy volunteers

Jain, Jay Prakash and Leong, Franz Joel Wen and Chen, Lanna and Kalluri, Sampath and Koradia, Vishal and Stein, Daniel and Wolf, Marie-Christine and Sunkara, Gangadhar and Kota, Jagannath (2017) Bioavailability of lumefantrine is significantly enhanced with a novel formulation approach, an outcome from a randomized, Open-label pharmacokinetic study in healthy volunteers. Antimicrobial Agents and Chemotherapy, 61 (9). ISSN 1098-6596

Abstract

The artemether-lumefantrine combination requires food intake for the optimal absorption of lumefantrine. In an attempt to enhance the 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, the relative bioavailability of the two SDF variants was compared with that of the conventional formulation after administration of a single dose of 480 mg under fasted conditions in three parallel cohorts. In part 2, the pharmacokinetics of lumefantrine from both SDF variants were 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 that of the conventional formulation. Both variants demonstrated a positive food effect and a less than proportional increase in exposure between the 480-mg and 960-mg doses. Most adverse events (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 in vital signs, electrocardiograms, or laboratory blood assessments were noted. The solid dispersion formulation enhances the lumefantrine bioavailability to a significant extent, and SDF variant 1 is superior to SDF variant 2.

Item Type: Article
Keywords: Antimalarial agents Bioavailability Lumefantrine Malaria Solid dispersion
Date Deposited: 26 Jan 2018 00:45
Last Modified: 25 Jan 2019 00:45
URI: https://oak.novartis.com/id/eprint/32118

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