Population pharmacokinetic assessment of the effect of food on piperaquine bioavailability in patients with uncomplicated malaria

TitlePopulation pharmacokinetic assessment of the effect of food on piperaquine bioavailability in patients with uncomplicated malaria
Publication TypeJournal Article
Year of Publication2014
AuthorsTarning, J, Lindegardh, N, Lwin, KMaung, Annerberg, A, Kiricharoen, L, Ashley, E, White, NJ, Nosten, F, Day, NPJ
JournalAntimicrob Agents Chemother
Volume58
Issue4
Pagination2052-2058
Date PublishedJanuary 21, 2014
Abstract

Previously published literature reports a varying impact 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 three days with (n=15) and without (n=15) concomitant food to patients with uncomplicated P. 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 a varying degree 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 the 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.

URLhttp://aac.asm.org/content/58/4/2052.full.pdf