Optimal designs for population pharmacokinetic studies of the partner drugs co-administered with artemisinin derivatives in patients with uncomplicated falciparum malaria
Abstract Background Artemisinin-based combination therapy (ACT) is currently recommended as first-line treatment for uncomplicated malaria, but of concern, it has been observed that the effectiveness of the main artemisinin derivative, artesunate, has been diminished due to parasite resistance. This...
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ftdoajarticles:oai:doaj.org/article:43ed78e6ad3b441584f7c2b82059d210 2023-05-15T15:13:45+02:00 Optimal designs for population pharmacokinetic studies of the partner drugs co-administered with artemisinin derivatives in patients with uncomplicated falciparum malaria Jamsen Kris M Duffull Stephen B Tarning Joel Lindegardh Niklas White Nicholas J Simpson Julie A 2012-07-01T00:00:00Z https://doi.org/10.1186/1475-2875-11-143 https://doaj.org/article/43ed78e6ad3b441584f7c2b82059d210 EN eng BMC http://www.malariajournal.com/content/11/1/143 https://doaj.org/toc/1475-2875 doi:10.1186/1475-2875-11-143 1475-2875 https://doaj.org/article/43ed78e6ad3b441584f7c2b82059d210 Malaria Journal, Vol 11, Iss 1, p 143 (2012) Artemisinin-based combination therapy Partner drugs Optimal design Arctic medicine. Tropical medicine RC955-962 Infectious and parasitic diseases RC109-216 article 2012 ftdoajarticles https://doi.org/10.1186/1475-2875-11-143 2022-12-31T08:35:42Z Abstract Background Artemisinin-based combination therapy (ACT) is currently recommended as first-line treatment for uncomplicated malaria, but of concern, it has been observed that the effectiveness of the main artemisinin derivative, artesunate, has been diminished due to parasite resistance. This reduction in effect highlights the importance of the partner drugs in ACT and provides motivation to gain more knowledge of their pharmacokinetic (PK) properties via population PK studies. Optimal design methodology has been developed for population PK studies, which analytically determines a sampling schedule that is clinically feasible and yields precise estimation of model parameters. In this work, optimal design methodology was used to determine sampling designs for typical future population PK studies of the partner drugs (mefloquine, lumefantrine, piperaquine and amodiaquine) co-administered with artemisinin derivatives. Methods The optimal designs were determined using freely available software and were based on structural PK models from the literature and the key specifications of 100 patients with five samples per patient, with one sample taken on the seventh day of treatment. The derived optimal designs were then evaluated via a simulation-estimation procedure. Results For all partner drugs, designs consisting of two sampling schedules (50 patients per schedule) with five samples per patient resulted in acceptable precision of the model parameter estimates. Conclusions The sampling schedules proposed in this paper should be considered in future population pharmacokinetic studies where intensive sampling over many days or weeks of follow-up is not possible due to either ethical, logistic or economical reasons. Article in Journal/Newspaper Arctic Directory of Open Access Journals: DOAJ Articles Arctic Malaria Journal 11 1 |
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Directory of Open Access Journals: DOAJ Articles |
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ftdoajarticles |
language |
English |
topic |
Artemisinin-based combination therapy Partner drugs Optimal design Arctic medicine. Tropical medicine RC955-962 Infectious and parasitic diseases RC109-216 |
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Artemisinin-based combination therapy Partner drugs Optimal design Arctic medicine. Tropical medicine RC955-962 Infectious and parasitic diseases RC109-216 Jamsen Kris M Duffull Stephen B Tarning Joel Lindegardh Niklas White Nicholas J Simpson Julie A Optimal designs for population pharmacokinetic studies of the partner drugs co-administered with artemisinin derivatives in patients with uncomplicated falciparum malaria |
topic_facet |
Artemisinin-based combination therapy Partner drugs Optimal design Arctic medicine. Tropical medicine RC955-962 Infectious and parasitic diseases RC109-216 |
description |
Abstract Background Artemisinin-based combination therapy (ACT) is currently recommended as first-line treatment for uncomplicated malaria, but of concern, it has been observed that the effectiveness of the main artemisinin derivative, artesunate, has been diminished due to parasite resistance. This reduction in effect highlights the importance of the partner drugs in ACT and provides motivation to gain more knowledge of their pharmacokinetic (PK) properties via population PK studies. Optimal design methodology has been developed for population PK studies, which analytically determines a sampling schedule that is clinically feasible and yields precise estimation of model parameters. In this work, optimal design methodology was used to determine sampling designs for typical future population PK studies of the partner drugs (mefloquine, lumefantrine, piperaquine and amodiaquine) co-administered with artemisinin derivatives. Methods The optimal designs were determined using freely available software and were based on structural PK models from the literature and the key specifications of 100 patients with five samples per patient, with one sample taken on the seventh day of treatment. The derived optimal designs were then evaluated via a simulation-estimation procedure. Results For all partner drugs, designs consisting of two sampling schedules (50 patients per schedule) with five samples per patient resulted in acceptable precision of the model parameter estimates. Conclusions The sampling schedules proposed in this paper should be considered in future population pharmacokinetic studies where intensive sampling over many days or weeks of follow-up is not possible due to either ethical, logistic or economical reasons. |
format |
Article in Journal/Newspaper |
author |
Jamsen Kris M Duffull Stephen B Tarning Joel Lindegardh Niklas White Nicholas J Simpson Julie A |
author_facet |
Jamsen Kris M Duffull Stephen B Tarning Joel Lindegardh Niklas White Nicholas J Simpson Julie A |
author_sort |
Jamsen Kris M |
title |
Optimal designs for population pharmacokinetic studies of the partner drugs co-administered with artemisinin derivatives in patients with uncomplicated falciparum malaria |
title_short |
Optimal designs for population pharmacokinetic studies of the partner drugs co-administered with artemisinin derivatives in patients with uncomplicated falciparum malaria |
title_full |
Optimal designs for population pharmacokinetic studies of the partner drugs co-administered with artemisinin derivatives in patients with uncomplicated falciparum malaria |
title_fullStr |
Optimal designs for population pharmacokinetic studies of the partner drugs co-administered with artemisinin derivatives in patients with uncomplicated falciparum malaria |
title_full_unstemmed |
Optimal designs for population pharmacokinetic studies of the partner drugs co-administered with artemisinin derivatives in patients with uncomplicated falciparum malaria |
title_sort |
optimal designs for population pharmacokinetic studies of the partner drugs co-administered with artemisinin derivatives in patients with uncomplicated falciparum malaria |
publisher |
BMC |
publishDate |
2012 |
url |
https://doi.org/10.1186/1475-2875-11-143 https://doaj.org/article/43ed78e6ad3b441584f7c2b82059d210 |
geographic |
Arctic |
geographic_facet |
Arctic |
genre |
Arctic |
genre_facet |
Arctic |
op_source |
Malaria Journal, Vol 11, Iss 1, p 143 (2012) |
op_relation |
http://www.malariajournal.com/content/11/1/143 https://doaj.org/toc/1475-2875 doi:10.1186/1475-2875-11-143 1475-2875 https://doaj.org/article/43ed78e6ad3b441584f7c2b82059d210 |
op_doi |
https://doi.org/10.1186/1475-2875-11-143 |
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Malaria Journal |
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11 |
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1 |
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