Population pharmacokinetic assessment of the effect of food on piperaquine bioavailability in patients with uncomplicated malaria
Title | Population pharmacokinetic assessment of the effect of food on piperaquine bioavailability in patients with uncomplicated malaria |
Publication Type | Journal Article |
Year of Publication | 2014 |
Authors | Tarning, J, Lindegardh, N, Lwin, KMaung, Annerberg, A, Kiricharoen, L, Ashley, E, White, NJ, Nosten, F, Day, NPJ |
Journal | Antimicrob Agents Chemother |
Volume | 58 |
Issue | 4 |
Pagination | 2052-2058 |
Date Published | January 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. |
URL | http://aac.asm.org/content/58/4/2052.full.pdf |