Cargando…
Population Pharmacokinetic Assessment of the Effect of Food on Piperaquine Bioavailability in Patients with Uncomplicated Malaria
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, ran...
Autores principales: | , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Society for Microbiology
2014
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4023753/ https://www.ncbi.nlm.nih.gov/pubmed/24449770 http://dx.doi.org/10.1128/AAC.02318-13 |
_version_ | 1782316582179962880 |
---|---|
author | Tarning, Joel Lindegardh, Niklas Lwin, Khin Maung Annerberg, Anna Kiricharoen, Lily Ashley, Elizabeth White, Nicholas J. Nosten, François Day, Nicholas P. J. |
author_facet | Tarning, Joel Lindegardh, Niklas Lwin, Khin Maung Annerberg, Anna Kiricharoen, Lily Ashley, Elizabeth White, Nicholas J. Nosten, François Day, Nicholas P. J. |
author_sort | Tarning, Joel |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-4023753 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | American Society for Microbiology |
record_format | MEDLINE/PubMed |
spelling | pubmed-40237532014-05-16 Population Pharmacokinetic Assessment of the Effect of Food on Piperaquine Bioavailability in Patients with Uncomplicated Malaria Tarning, Joel Lindegardh, Niklas Lwin, Khin Maung Annerberg, Anna Kiricharoen, Lily Ashley, Elizabeth White, Nicholas J. Nosten, François Day, Nicholas P. J. Antimicrob Agents Chemother Pharmacology 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. American Society for Microbiology 2014-04 /pmc/articles/PMC4023753/ /pubmed/24449770 http://dx.doi.org/10.1128/AAC.02318-13 Text en Copyright © 2014 Tarning et al. http://creativecommons.org/licenses/by/3.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution 3.0 Unported license (http://creativecommons.org/licenses/by/3.0/) . |
spellingShingle | Pharmacology Tarning, Joel Lindegardh, Niklas Lwin, Khin Maung Annerberg, Anna Kiricharoen, Lily Ashley, Elizabeth White, Nicholas J. Nosten, François Day, Nicholas P. J. 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 |
title_full | Population Pharmacokinetic Assessment of the Effect of Food on Piperaquine Bioavailability in Patients with Uncomplicated Malaria |
title_fullStr | Population Pharmacokinetic Assessment of the Effect of Food on Piperaquine Bioavailability in Patients with Uncomplicated Malaria |
title_full_unstemmed | Population Pharmacokinetic Assessment of the Effect of Food on Piperaquine Bioavailability in Patients with Uncomplicated Malaria |
title_short | Population Pharmacokinetic Assessment of the Effect of Food on Piperaquine Bioavailability in Patients with Uncomplicated Malaria |
title_sort | population pharmacokinetic assessment of the effect of food on piperaquine bioavailability in patients with uncomplicated malaria |
topic | Pharmacology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4023753/ https://www.ncbi.nlm.nih.gov/pubmed/24449770 http://dx.doi.org/10.1128/AAC.02318-13 |
work_keys_str_mv | AT tarningjoel populationpharmacokineticassessmentoftheeffectoffoodonpiperaquinebioavailabilityinpatientswithuncomplicatedmalaria AT lindegardhniklas populationpharmacokineticassessmentoftheeffectoffoodonpiperaquinebioavailabilityinpatientswithuncomplicatedmalaria AT lwinkhinmaung populationpharmacokineticassessmentoftheeffectoffoodonpiperaquinebioavailabilityinpatientswithuncomplicatedmalaria AT annerberganna populationpharmacokineticassessmentoftheeffectoffoodonpiperaquinebioavailabilityinpatientswithuncomplicatedmalaria AT kiricharoenlily populationpharmacokineticassessmentoftheeffectoffoodonpiperaquinebioavailabilityinpatientswithuncomplicatedmalaria AT ashleyelizabeth populationpharmacokineticassessmentoftheeffectoffoodonpiperaquinebioavailabilityinpatientswithuncomplicatedmalaria AT whitenicholasj populationpharmacokineticassessmentoftheeffectoffoodonpiperaquinebioavailabilityinpatientswithuncomplicatedmalaria AT nostenfrancois populationpharmacokineticassessmentoftheeffectoffoodonpiperaquinebioavailabilityinpatientswithuncomplicatedmalaria AT daynicholaspj populationpharmacokineticassessmentoftheeffectoffoodonpiperaquinebioavailabilityinpatientswithuncomplicatedmalaria |