A population pharmacokinetic model of piperaquine in pregnant and non-pregnant women with uncomplicated Plasmodium falciparum malaria in Sudan
Abstract Background Pregnancy is associated with an increased risk of developing a malaria infection and a higher risk of developing severe malaria. The pharmacokinetic properties of many anti-malarials are also altered during pregnancy, often resulting in a decreased drug exposure. Piperaquine is a...
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ftdoajarticles:oai:doaj.org/article:7fc1e315940a4829b942c8c7e04390e2 2023-05-15T15:14:18+02:00 A population pharmacokinetic model of piperaquine in pregnant and non-pregnant women with uncomplicated Plasmodium falciparum malaria in Sudan Hoglund Richard M Adam Ishag Hanpithakpong Warunee Ashton Michael Lindegardh Niklas Day Nicholas PJ White Nicholas J Nosten Francois Tarning Joel 2012-11-01T00:00:00Z https://doi.org/10.1186/1475-2875-11-398 https://doaj.org/article/7fc1e315940a4829b942c8c7e04390e2 EN eng BMC http://www.malariajournal.com/content/11/1/398 https://doaj.org/toc/1475-2875 doi:10.1186/1475-2875-11-398 1475-2875 https://doaj.org/article/7fc1e315940a4829b942c8c7e04390e2 Malaria Journal, Vol 11, Iss 1, p 398 (2012) Malaria Piperaquine Pregnancy Population pharmacokinetics Nonlinear mixed-effects modelling Arctic medicine. Tropical medicine RC955-962 Infectious and parasitic diseases RC109-216 article 2012 ftdoajarticles https://doi.org/10.1186/1475-2875-11-398 2022-12-31T13:50:01Z Abstract Background Pregnancy is associated with an increased risk of developing a malaria infection and a higher risk of developing severe malaria. The pharmacokinetic properties of many anti-malarials are also altered during pregnancy, often resulting in a decreased drug exposure. Piperaquine is a promising anti-malarial partner drug used in a fixed-dose combination with dihydroartemisinin. The aim of this study was to investigate the population pharmacokinetics of piperaquine in pregnant and non-pregnant Sudanese women with uncomplicated Plasmodium falciparum malaria. Method Symptomatic patients received a standard dose regimen of the fixed dose oral piperaquine-dihydroartemisinin combination treatment. Densely sampled plasma aliquots were collected and analysed using a previously described LC-MS/MS method. Data from 12 pregnant and 12 non-pregnant women were analysed using nonlinear mixed-effects modelling. A Monte Carlo Mapped Power (MCMP) analysis was conducted based on a previously published study to evaluate the power of detecting covariates in this relatively small study. Results A three-compartment disposition model with a transit-absorption model described the observed data well. Body weight was added as an allometric function on all clearance and volume parameters. A statistically significant decrease in estimated terminal piperaquine half-life in pregnant compared with non-pregnant women was found, but there were no differences in post-hoc estimates of total piperaquine exposure. The MCMP analysis indicated a minimum of 13 pregnant and 13 non-pregnant women were required to identify pregnancy as a covariate on relevant pharmacokinetic parameters (80% power and p=0.05). Pregnancy was, therefore, evaluated as a categorical and continuous covariate (i.e. estimate gestational age) in a full covariate approach. Using this approach pregnancy was not associated with any major change in piperaquine elimination clearance. However, a trend of increasing elimination clearance with increasing gestational age ... Article in Journal/Newspaper Arctic Directory of Open Access Journals: DOAJ Articles Arctic Malaria Journal 11 1 398 |
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Directory of Open Access Journals: DOAJ Articles |
op_collection_id |
ftdoajarticles |
language |
English |
topic |
Malaria Piperaquine Pregnancy Population pharmacokinetics Nonlinear mixed-effects modelling Arctic medicine. Tropical medicine RC955-962 Infectious and parasitic diseases RC109-216 |
spellingShingle |
Malaria Piperaquine Pregnancy Population pharmacokinetics Nonlinear mixed-effects modelling Arctic medicine. Tropical medicine RC955-962 Infectious and parasitic diseases RC109-216 Hoglund Richard M Adam Ishag Hanpithakpong Warunee Ashton Michael Lindegardh Niklas Day Nicholas PJ White Nicholas J Nosten Francois Tarning Joel A population pharmacokinetic model of piperaquine in pregnant and non-pregnant women with uncomplicated Plasmodium falciparum malaria in Sudan |
topic_facet |
Malaria Piperaquine Pregnancy Population pharmacokinetics Nonlinear mixed-effects modelling Arctic medicine. Tropical medicine RC955-962 Infectious and parasitic diseases RC109-216 |
description |
Abstract Background Pregnancy is associated with an increased risk of developing a malaria infection and a higher risk of developing severe malaria. The pharmacokinetic properties of many anti-malarials are also altered during pregnancy, often resulting in a decreased drug exposure. Piperaquine is a promising anti-malarial partner drug used in a fixed-dose combination with dihydroartemisinin. The aim of this study was to investigate the population pharmacokinetics of piperaquine in pregnant and non-pregnant Sudanese women with uncomplicated Plasmodium falciparum malaria. Method Symptomatic patients received a standard dose regimen of the fixed dose oral piperaquine-dihydroartemisinin combination treatment. Densely sampled plasma aliquots were collected and analysed using a previously described LC-MS/MS method. Data from 12 pregnant and 12 non-pregnant women were analysed using nonlinear mixed-effects modelling. A Monte Carlo Mapped Power (MCMP) analysis was conducted based on a previously published study to evaluate the power of detecting covariates in this relatively small study. Results A three-compartment disposition model with a transit-absorption model described the observed data well. Body weight was added as an allometric function on all clearance and volume parameters. A statistically significant decrease in estimated terminal piperaquine half-life in pregnant compared with non-pregnant women was found, but there were no differences in post-hoc estimates of total piperaquine exposure. The MCMP analysis indicated a minimum of 13 pregnant and 13 non-pregnant women were required to identify pregnancy as a covariate on relevant pharmacokinetic parameters (80% power and p=0.05). Pregnancy was, therefore, evaluated as a categorical and continuous covariate (i.e. estimate gestational age) in a full covariate approach. Using this approach pregnancy was not associated with any major change in piperaquine elimination clearance. However, a trend of increasing elimination clearance with increasing gestational age ... |
format |
Article in Journal/Newspaper |
author |
Hoglund Richard M Adam Ishag Hanpithakpong Warunee Ashton Michael Lindegardh Niklas Day Nicholas PJ White Nicholas J Nosten Francois Tarning Joel |
author_facet |
Hoglund Richard M Adam Ishag Hanpithakpong Warunee Ashton Michael Lindegardh Niklas Day Nicholas PJ White Nicholas J Nosten Francois Tarning Joel |
author_sort |
Hoglund Richard M |
title |
A population pharmacokinetic model of piperaquine in pregnant and non-pregnant women with uncomplicated Plasmodium falciparum malaria in Sudan |
title_short |
A population pharmacokinetic model of piperaquine in pregnant and non-pregnant women with uncomplicated Plasmodium falciparum malaria in Sudan |
title_full |
A population pharmacokinetic model of piperaquine in pregnant and non-pregnant women with uncomplicated Plasmodium falciparum malaria in Sudan |
title_fullStr |
A population pharmacokinetic model of piperaquine in pregnant and non-pregnant women with uncomplicated Plasmodium falciparum malaria in Sudan |
title_full_unstemmed |
A population pharmacokinetic model of piperaquine in pregnant and non-pregnant women with uncomplicated Plasmodium falciparum malaria in Sudan |
title_sort |
population pharmacokinetic model of piperaquine in pregnant and non-pregnant women with uncomplicated plasmodium falciparum malaria in sudan |
publisher |
BMC |
publishDate |
2012 |
url |
https://doi.org/10.1186/1475-2875-11-398 https://doaj.org/article/7fc1e315940a4829b942c8c7e04390e2 |
geographic |
Arctic |
geographic_facet |
Arctic |
genre |
Arctic |
genre_facet |
Arctic |
op_source |
Malaria Journal, Vol 11, Iss 1, p 398 (2012) |
op_relation |
http://www.malariajournal.com/content/11/1/398 https://doaj.org/toc/1475-2875 doi:10.1186/1475-2875-11-398 1475-2875 https://doaj.org/article/7fc1e315940a4829b942c8c7e04390e2 |
op_doi |
https://doi.org/10.1186/1475-2875-11-398 |
container_title |
Malaria Journal |
container_volume |
11 |
container_issue |
1 |
container_start_page |
398 |
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1766344766727913472 |