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Pharmacokinetics‐Pharmacodynamics of High‐Dose Ivermectin with Dihydroartemisinin‐Piperaquine on Mosquitocidal Activity and QT‐Prolongation (IVERMAL)
High‐dose ivermectin, co‐administered for 3 days with dihydroartemisinin‐piperaquine (DP), killed mosquitoes feeding on individuals for at least 28 days posttreatment in a recent trial (IVERMAL), whereas 7 days was predicted pretrial. The current study assessed the relationship between ivermectin bl...
Autores principales: | , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6585895/ https://www.ncbi.nlm.nih.gov/pubmed/30125353 http://dx.doi.org/10.1002/cpt.1219 |
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author | Smit, Menno R. Ochomo, Eric O. Waterhouse, David Kwambai, Titus K. Abong'o, Bernard O. Bousema, Teun Bayoh, Nabie M. Gimnig, John E. Samuels, Aaron M. Desai, Meghna R. Phillips‐Howard, Penelope A. Kariuki, Simon K. Wang, Duolao ter Kuile, Feiko O. Ward, Stephen A. Aljayyoussi, Ghaith |
author_facet | Smit, Menno R. Ochomo, Eric O. Waterhouse, David Kwambai, Titus K. Abong'o, Bernard O. Bousema, Teun Bayoh, Nabie M. Gimnig, John E. Samuels, Aaron M. Desai, Meghna R. Phillips‐Howard, Penelope A. Kariuki, Simon K. Wang, Duolao ter Kuile, Feiko O. Ward, Stephen A. Aljayyoussi, Ghaith |
author_sort | Smit, Menno R. |
collection | PubMed |
description | High‐dose ivermectin, co‐administered for 3 days with dihydroartemisinin‐piperaquine (DP), killed mosquitoes feeding on individuals for at least 28 days posttreatment in a recent trial (IVERMAL), whereas 7 days was predicted pretrial. The current study assessed the relationship between ivermectin blood concentrations and the observed mosquitocidal effects against Anopheles gambiae s.s. Three days of ivermectin 0, 300, or 600 mcg/kg/day plus DP was randomly assigned to 141 adults with uncomplicated malaria in Kenya. During 28 days of follow‐up, 1,393 venous and 335 paired capillary plasma samples, 850 mosquito‐cluster mortality rates, and 524 QTcF‐intervals were collected. Using pharmacokinetic/pharmacodynamic (PK/PD) modeling, we show a consistent correlation between predicted ivermectin concentrations and observed mosquitocidal‐effects throughout the 28‐day study duration, without invoking an unidentified mosquitocidal metabolite or drug‐drug interaction. Ivermectin had no effect on piperaquine's PKs or QTcF‐prolongation. The PK/PD model can be used to design new treatment regimens with predicted mosquitocidal effect. This methodology could be used to evaluate effectiveness of other endectocides. |
format | Online Article Text |
id | pubmed-6585895 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-65858952019-06-27 Pharmacokinetics‐Pharmacodynamics of High‐Dose Ivermectin with Dihydroartemisinin‐Piperaquine on Mosquitocidal Activity and QT‐Prolongation (IVERMAL) Smit, Menno R. Ochomo, Eric O. Waterhouse, David Kwambai, Titus K. Abong'o, Bernard O. Bousema, Teun Bayoh, Nabie M. Gimnig, John E. Samuels, Aaron M. Desai, Meghna R. Phillips‐Howard, Penelope A. Kariuki, Simon K. Wang, Duolao ter Kuile, Feiko O. Ward, Stephen A. Aljayyoussi, Ghaith Clin Pharmacol Ther Research High‐dose ivermectin, co‐administered for 3 days with dihydroartemisinin‐piperaquine (DP), killed mosquitoes feeding on individuals for at least 28 days posttreatment in a recent trial (IVERMAL), whereas 7 days was predicted pretrial. The current study assessed the relationship between ivermectin blood concentrations and the observed mosquitocidal effects against Anopheles gambiae s.s. Three days of ivermectin 0, 300, or 600 mcg/kg/day plus DP was randomly assigned to 141 adults with uncomplicated malaria in Kenya. During 28 days of follow‐up, 1,393 venous and 335 paired capillary plasma samples, 850 mosquito‐cluster mortality rates, and 524 QTcF‐intervals were collected. Using pharmacokinetic/pharmacodynamic (PK/PD) modeling, we show a consistent correlation between predicted ivermectin concentrations and observed mosquitocidal‐effects throughout the 28‐day study duration, without invoking an unidentified mosquitocidal metabolite or drug‐drug interaction. Ivermectin had no effect on piperaquine's PKs or QTcF‐prolongation. The PK/PD model can be used to design new treatment regimens with predicted mosquitocidal effect. This methodology could be used to evaluate effectiveness of other endectocides. John Wiley and Sons Inc. 2018-10-09 2019-02 /pmc/articles/PMC6585895/ /pubmed/30125353 http://dx.doi.org/10.1002/cpt.1219 Text en © 2018 The Authors Clinical Pharmacology & Therapeutics published by Wiley Periodicals, Inc. on behalf of American Society for Clinical Pharmacology and Therapeutics This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes. |
spellingShingle | Research Smit, Menno R. Ochomo, Eric O. Waterhouse, David Kwambai, Titus K. Abong'o, Bernard O. Bousema, Teun Bayoh, Nabie M. Gimnig, John E. Samuels, Aaron M. Desai, Meghna R. Phillips‐Howard, Penelope A. Kariuki, Simon K. Wang, Duolao ter Kuile, Feiko O. Ward, Stephen A. Aljayyoussi, Ghaith Pharmacokinetics‐Pharmacodynamics of High‐Dose Ivermectin with Dihydroartemisinin‐Piperaquine on Mosquitocidal Activity and QT‐Prolongation (IVERMAL) |
title | Pharmacokinetics‐Pharmacodynamics of High‐Dose Ivermectin with Dihydroartemisinin‐Piperaquine on Mosquitocidal Activity and QT‐Prolongation (IVERMAL) |
title_full | Pharmacokinetics‐Pharmacodynamics of High‐Dose Ivermectin with Dihydroartemisinin‐Piperaquine on Mosquitocidal Activity and QT‐Prolongation (IVERMAL) |
title_fullStr | Pharmacokinetics‐Pharmacodynamics of High‐Dose Ivermectin with Dihydroartemisinin‐Piperaquine on Mosquitocidal Activity and QT‐Prolongation (IVERMAL) |
title_full_unstemmed | Pharmacokinetics‐Pharmacodynamics of High‐Dose Ivermectin with Dihydroartemisinin‐Piperaquine on Mosquitocidal Activity and QT‐Prolongation (IVERMAL) |
title_short | Pharmacokinetics‐Pharmacodynamics of High‐Dose Ivermectin with Dihydroartemisinin‐Piperaquine on Mosquitocidal Activity and QT‐Prolongation (IVERMAL) |
title_sort | pharmacokinetics‐pharmacodynamics of high‐dose ivermectin with dihydroartemisinin‐piperaquine on mosquitocidal activity and qt‐prolongation (ivermal) |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6585895/ https://www.ncbi.nlm.nih.gov/pubmed/30125353 http://dx.doi.org/10.1002/cpt.1219 |
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