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Please use this identifier to cite or link to this item: http://repository.li.mahidol.ac.th/dspace/handle/123456789/34727
Title: Population pharmacokinetic assessment of the effect of food on piperaquine bioavailability in patients with uncomplicated malaria
Authors: Joel Tarning
Niklas Lindegardh
Khin Maung Lwin
Anna Annerberg
Lily Kiricharoen
Elizabeth Ashley
Nicholas J. White
François Nosten
Nicholas P.J. Day
Mahidol University
Nuffield Department of Clinical Medicine
Keywords: Medicine;Pharmacology, Toxicology and Pharmaceutics
Issue Date: 1-Jan-2014
Citation: Antimicrobial Agents and Chemotherapy. Vol.58, No.4 (2014), 2052-2058
Abstract: Previously published literature reports various impacts of food on the oral bioavailability of piperaquine. The aim of this study was to use a population modeling approach to investigate the impact of concomitant intake of a small amount of food on piperaquine pharmacokinetics. This was an open, randomized comparison of piperaquine pharmacokinetics when administered as a fixed oral formulation once daily for 3 days with (n = 15) and without (n = 15) concomitant food to patients with uncomplicated Plasmodium falciparum malaria in Thailand. Nonlinear mixed-effects modeling was used to characterize the pharmacokinetics of piperaquine and the influence of concomitant food intake. A modified Monte Carlo mapped power approach was applied to evaluate the relationship between statistical power and various degrees of covariate effect sizes of the given study design. Piperaquine population pharmacokinetics were described well in fasting and fed patients by a three-compartment distribution model with flexible absorption. The final model showed a 25% increase in relative bioavailability per dose occasion during recovery from malaria but demonstrated no clinical impact of concomitant intake of a low-fat meal. Body weight and age were both significant covariates in the final model. The novel power approach concluded that the study was adequately powered to detect a food effect of at least 35%. This modified Monte Carlo mapped power approach may be a useful tool for evaluating the power to detect true covariate effects in mixed-effects modeling and a given study design. A small amount of food does not affect piperaquine absorption significantly in acute malaria. Copyright © 2014 Tarning et al.
URI: https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=84896981219&origin=inward
http://repository.li.mahidol.ac.th/dspace/handle/123456789/34727
ISSN: 10986596
00664804
Appears in Collections:Scopus 2011-2015

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