Optimal designs for population pharmacokinetic studies of oral artesunate in patients with uncomplicated falciparum malaria
Abstract Background Currently, population pharmacokinetic (PK) studies of anti-malarial drugs are designed primarily by the logistical and ethical constraints of taking blood samples from patients, and the statistical models that are fitted to the data are not formally considered. This could lead to...
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ftdoajarticles:oai:doaj.org/article:24c9d051e82d49488394453ce728a0ba 2023-05-15T15:15:46+02:00 Optimal designs for population pharmacokinetic studies of oral artesunate in patients with uncomplicated falciparum malaria Lindegardh Niklas Tarning Joel Duffull Stephen B Jamsen Kris M White Nicholas J Simpson Julie A 2011-07-01T00:00:00Z https://doi.org/10.1186/1475-2875-10-181 https://doaj.org/article/24c9d051e82d49488394453ce728a0ba EN eng BMC http://www.malariajournal.com/content/10/1/181 https://doaj.org/toc/1475-2875 doi:10.1186/1475-2875-10-181 1475-2875 https://doaj.org/article/24c9d051e82d49488394453ce728a0ba Malaria Journal, Vol 10, Iss 1, p 181 (2011) Arctic medicine. Tropical medicine RC955-962 Infectious and parasitic diseases RC109-216 article 2011 ftdoajarticles https://doi.org/10.1186/1475-2875-10-181 2022-12-31T09:33:41Z Abstract Background Currently, population pharmacokinetic (PK) studies of anti-malarial drugs are designed primarily by the logistical and ethical constraints of taking blood samples from patients, and the statistical models that are fitted to the data are not formally considered. This could lead to imprecise estimates of the target PK parameters, and/or designs insufficient to estimate all of the parameters. Optimal design methodology has been developed to determine blood sampling schedules that will yield precise parameter estimates within the practical constraints of sampling the study populations. In this work optimal design methods were used to determine sampling designs for typical future population PK studies of dihydroartemisinin, the principal biologically active metabolite of oral artesunate. Methods Optimal designs were derived using freely available software and were based on appropriate structural PK models from an analysis of data or the literature and key sampling constraints identified in a questionnaire sent to active malaria researchers (3-4 samples per patient, at least 15 minutes between samples). The derived optimal designs were then evaluated via simulation-estimation. Results The derived optimal sampling windows were 17 to 29 minutes, 30 to 57 minutes, 2.5 to 3.7 hours and 5.8 to 6.6 hours for non-pregnant adults; 16 to 29 minutes, 31 minutes to 1 hour, 2.0 to 3.4 hours and 5.5 to 6.6 hours for designs with non-pregnant adults and children and 35 to 59 minutes, 1.2 to 3.4 hours, 3.4 to 4.9 hours and 6.0 to 8.0 hours for pregnant women. The optimal designs resulted in acceptable precision of the PK parameters. Conclusions The proposed sampling designs in this paper are robust and efficient and should be considered in future PK studies of oral artesunate where only three or four blood samples can be collected. Article in Journal/Newspaper Arctic Directory of Open Access Journals: DOAJ Articles Arctic Malaria Journal 10 1 |
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Directory of Open Access Journals: DOAJ Articles |
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Arctic medicine. Tropical medicine RC955-962 Infectious and parasitic diseases RC109-216 |
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Arctic medicine. Tropical medicine RC955-962 Infectious and parasitic diseases RC109-216 Lindegardh Niklas Tarning Joel Duffull Stephen B Jamsen Kris M White Nicholas J Simpson Julie A Optimal designs for population pharmacokinetic studies of oral artesunate in patients with uncomplicated falciparum malaria |
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Arctic medicine. Tropical medicine RC955-962 Infectious and parasitic diseases RC109-216 |
description |
Abstract Background Currently, population pharmacokinetic (PK) studies of anti-malarial drugs are designed primarily by the logistical and ethical constraints of taking blood samples from patients, and the statistical models that are fitted to the data are not formally considered. This could lead to imprecise estimates of the target PK parameters, and/or designs insufficient to estimate all of the parameters. Optimal design methodology has been developed to determine blood sampling schedules that will yield precise parameter estimates within the practical constraints of sampling the study populations. In this work optimal design methods were used to determine sampling designs for typical future population PK studies of dihydroartemisinin, the principal biologically active metabolite of oral artesunate. Methods Optimal designs were derived using freely available software and were based on appropriate structural PK models from an analysis of data or the literature and key sampling constraints identified in a questionnaire sent to active malaria researchers (3-4 samples per patient, at least 15 minutes between samples). The derived optimal designs were then evaluated via simulation-estimation. Results The derived optimal sampling windows were 17 to 29 minutes, 30 to 57 minutes, 2.5 to 3.7 hours and 5.8 to 6.6 hours for non-pregnant adults; 16 to 29 minutes, 31 minutes to 1 hour, 2.0 to 3.4 hours and 5.5 to 6.6 hours for designs with non-pregnant adults and children and 35 to 59 minutes, 1.2 to 3.4 hours, 3.4 to 4.9 hours and 6.0 to 8.0 hours for pregnant women. The optimal designs resulted in acceptable precision of the PK parameters. Conclusions The proposed sampling designs in this paper are robust and efficient and should be considered in future PK studies of oral artesunate where only three or four blood samples can be collected. |
format |
Article in Journal/Newspaper |
author |
Lindegardh Niklas Tarning Joel Duffull Stephen B Jamsen Kris M White Nicholas J Simpson Julie A |
author_facet |
Lindegardh Niklas Tarning Joel Duffull Stephen B Jamsen Kris M White Nicholas J Simpson Julie A |
author_sort |
Lindegardh Niklas |
title |
Optimal designs for population pharmacokinetic studies of oral artesunate in patients with uncomplicated falciparum malaria |
title_short |
Optimal designs for population pharmacokinetic studies of oral artesunate in patients with uncomplicated falciparum malaria |
title_full |
Optimal designs for population pharmacokinetic studies of oral artesunate in patients with uncomplicated falciparum malaria |
title_fullStr |
Optimal designs for population pharmacokinetic studies of oral artesunate in patients with uncomplicated falciparum malaria |
title_full_unstemmed |
Optimal designs for population pharmacokinetic studies of oral artesunate in patients with uncomplicated falciparum malaria |
title_sort |
optimal designs for population pharmacokinetic studies of oral artesunate in patients with uncomplicated falciparum malaria |
publisher |
BMC |
publishDate |
2011 |
url |
https://doi.org/10.1186/1475-2875-10-181 https://doaj.org/article/24c9d051e82d49488394453ce728a0ba |
geographic |
Arctic |
geographic_facet |
Arctic |
genre |
Arctic |
genre_facet |
Arctic |
op_source |
Malaria Journal, Vol 10, Iss 1, p 181 (2011) |
op_relation |
http://www.malariajournal.com/content/10/1/181 https://doaj.org/toc/1475-2875 doi:10.1186/1475-2875-10-181 1475-2875 https://doaj.org/article/24c9d051e82d49488394453ce728a0ba |
op_doi |
https://doi.org/10.1186/1475-2875-10-181 |
container_title |
Malaria Journal |
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10 |
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1 |
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1766346104959401984 |