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Population Pharmacokinetics and Antimalarial Pharmacodynamics of Piperaquine in Patients With Plasmodium vivax Malaria in Thailand

Dihydroartemisinin-piperaquine is an effective drug in the treatment of Plasmodium falciparum and P. vivax malaria. The objective of this study was to evaluate the population pharmacokinetics and pharmacodynamics of piperaquine in patients with P. vivax malaria in Thailand after a standard regimen o...

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Autores principales: Tarning, J, Thana, P, Phyo, A P, Lwin, K M, Hanpithakpong, W, Ashley, E A, Day, N P J, Nosten, F, White, N J
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4150927/
https://www.ncbi.nlm.nih.gov/pubmed/25163024
http://dx.doi.org/10.1038/psp.2014.29
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author Tarning, J
Thana, P
Phyo, A P
Lwin, K M
Hanpithakpong, W
Ashley, E A
Day, N P J
Nosten, F
White, N J
author_facet Tarning, J
Thana, P
Phyo, A P
Lwin, K M
Hanpithakpong, W
Ashley, E A
Day, N P J
Nosten, F
White, N J
author_sort Tarning, J
collection PubMed
description Dihydroartemisinin-piperaquine is an effective drug in the treatment of Plasmodium falciparum and P. vivax malaria. The objective of this study was to evaluate the population pharmacokinetics and pharmacodynamics of piperaquine in patients with P. vivax malaria in Thailand after a standard regimen of dihydroartemisinin-piperaquine to determine whether residual piperaquine prevents or delays the emergence of P. vivax relapse. Sparse blood samples were collected from 116 patients. Piperaquine pharmacokinetics were described well by a three-compartment distribution model. Relapsing P. vivax malaria was accommodated by a constant baseline hazard (8.94 relapses/year) with the addition of a surge function in a fixed 3-week interval and a protective piperaquine effect. The results suggest that a large proportion of the first relapses were suppressed completely by residual piperaquine concentrations and that recurrences resulted mainly from emergence of the second or third relapse or from reinfection. This suggests a significant reduction in P. vivax morbidity when using dihydroartemisinin-piperaquine compared with other antimalarial drugs with shorter terminal postprophylactic effects.
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spelling pubmed-41509272014-09-04 Population Pharmacokinetics and Antimalarial Pharmacodynamics of Piperaquine in Patients With Plasmodium vivax Malaria in Thailand Tarning, J Thana, P Phyo, A P Lwin, K M Hanpithakpong, W Ashley, E A Day, N P J Nosten, F White, N J CPT Pharmacometrics Syst Pharmacol Original Article Dihydroartemisinin-piperaquine is an effective drug in the treatment of Plasmodium falciparum and P. vivax malaria. The objective of this study was to evaluate the population pharmacokinetics and pharmacodynamics of piperaquine in patients with P. vivax malaria in Thailand after a standard regimen of dihydroartemisinin-piperaquine to determine whether residual piperaquine prevents or delays the emergence of P. vivax relapse. Sparse blood samples were collected from 116 patients. Piperaquine pharmacokinetics were described well by a three-compartment distribution model. Relapsing P. vivax malaria was accommodated by a constant baseline hazard (8.94 relapses/year) with the addition of a surge function in a fixed 3-week interval and a protective piperaquine effect. The results suggest that a large proportion of the first relapses were suppressed completely by residual piperaquine concentrations and that recurrences resulted mainly from emergence of the second or third relapse or from reinfection. This suggests a significant reduction in P. vivax morbidity when using dihydroartemisinin-piperaquine compared with other antimalarial drugs with shorter terminal postprophylactic effects. Nature Publishing Group 2014-08 2014-08-27 /pmc/articles/PMC4150927/ /pubmed/25163024 http://dx.doi.org/10.1038/psp.2014.29 Text en Copyright © 2014 American Society for Clinical Pharmacology and Therapeutics http://creativecommons.org/licenses/by/3.0/ This work is licensed under a Creative Commons Attribution 3.0 Unported License The images or other third party material in this article are included in the article's Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/3.0/
spellingShingle Original Article
Tarning, J
Thana, P
Phyo, A P
Lwin, K M
Hanpithakpong, W
Ashley, E A
Day, N P J
Nosten, F
White, N J
Population Pharmacokinetics and Antimalarial Pharmacodynamics of Piperaquine in Patients With Plasmodium vivax Malaria in Thailand
title Population Pharmacokinetics and Antimalarial Pharmacodynamics of Piperaquine in Patients With Plasmodium vivax Malaria in Thailand
title_full Population Pharmacokinetics and Antimalarial Pharmacodynamics of Piperaquine in Patients With Plasmodium vivax Malaria in Thailand
title_fullStr Population Pharmacokinetics and Antimalarial Pharmacodynamics of Piperaquine in Patients With Plasmodium vivax Malaria in Thailand
title_full_unstemmed Population Pharmacokinetics and Antimalarial Pharmacodynamics of Piperaquine in Patients With Plasmodium vivax Malaria in Thailand
title_short Population Pharmacokinetics and Antimalarial Pharmacodynamics of Piperaquine in Patients With Plasmodium vivax Malaria in Thailand
title_sort population pharmacokinetics and antimalarial pharmacodynamics of piperaquine in patients with plasmodium vivax malaria in thailand
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4150927/
https://www.ncbi.nlm.nih.gov/pubmed/25163024
http://dx.doi.org/10.1038/psp.2014.29
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