Population pharmacokinetics of ivermectin for the treatment of scabies in Indigenous Australian children.
Ivermectin is a broad-spectrum antiparasitic agent used for the treatment and control of neglected tropical diseases. In Australia, ivermectin is primarily used for scabies and is licensed in children aged ≥5 years weighing >15 kg. However, young children, aged <5 years, are particularly vulne...
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ftdoajarticles:oai:doaj.org/article:e2c4720eb4d2415a8b78655c4b9e07b8 2023-05-15T15:15:44+02:00 Population pharmacokinetics of ivermectin for the treatment of scabies in Indigenous Australian children. Amanda Gwee Stephen Duffull Xiao Zhu Steven Y C Tong Noel Cranswick Brett McWhinney Jacobus Ungerer Joshua Francis Andrew C Steer 2020-12-01T00:00:00Z https://doi.org/10.1371/journal.pntd.0008886 https://doaj.org/article/e2c4720eb4d2415a8b78655c4b9e07b8 EN eng Public Library of Science (PLoS) https://doi.org/10.1371/journal.pntd.0008886 https://doaj.org/toc/1935-2727 https://doaj.org/toc/1935-2735 1935-2727 1935-2735 doi:10.1371/journal.pntd.0008886 https://doaj.org/article/e2c4720eb4d2415a8b78655c4b9e07b8 PLoS Neglected Tropical Diseases, Vol 14, Iss 12, p e0008886 (2020) Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 article 2020 ftdoajarticles https://doi.org/10.1371/journal.pntd.0008886 2022-12-31T15:17:02Z Ivermectin is a broad-spectrum antiparasitic agent used for the treatment and control of neglected tropical diseases. In Australia, ivermectin is primarily used for scabies and is licensed in children aged ≥5 years weighing >15 kg. However, young children, aged <5 years, are particularly vulnerable to scabies and its secondary complications. Therefore, this study aimed to determine an appropriate ivermectin dose for children aged 2 to 4 years and weighing ≤15 kg. We conducted a prospective, pharmacokinetic study of ivermectin in Indigenous Australian children aged between 5 and 15 years and weighing >15 kg. Doses of 200 μg/kg rounded to the nearest whole or half 3 mg tablet were given to children with scabies and ivermectin concentrations determined at two time points after dosing. A population pharmacokinetic model was developed using non-linear mixed effects modelling. A separate covariate database of children aged 2 to 4 years and weighing <15 kg was used to generate 1000 virtual patients and simulate the dose required to achieve equivalent drug exposure in young children as those aged ≥5 years. Overall, 26 children who had 48 ivermectin concentrations determined were included, 11 (42%) were male, the median age was 10.9 years and median body weight 37.6 kg. The final model was a two-compartment model with first-order absorption and linear elimination. For simulated children aged 2 to 4 years, a dose of 3 mg in children weighing 10-15 kg produced similar drug exposures to those >5 years. The median simulated area under the concentration-time curve was 976 μg∙h/L. Using modelling, we have identified a dosing strategy for ivermectin in children aged 2 to 4 years and weighing less than 15 kg that can be prospectively evaluated for safety and efficacy. Article in Journal/Newspaper Arctic Directory of Open Access Journals: DOAJ Articles Arctic PLOS Neglected Tropical Diseases 14 12 e0008886 |
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Directory of Open Access Journals: DOAJ Articles |
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English |
topic |
Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 |
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Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 Amanda Gwee Stephen Duffull Xiao Zhu Steven Y C Tong Noel Cranswick Brett McWhinney Jacobus Ungerer Joshua Francis Andrew C Steer Population pharmacokinetics of ivermectin for the treatment of scabies in Indigenous Australian children. |
topic_facet |
Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 |
description |
Ivermectin is a broad-spectrum antiparasitic agent used for the treatment and control of neglected tropical diseases. In Australia, ivermectin is primarily used for scabies and is licensed in children aged ≥5 years weighing >15 kg. However, young children, aged <5 years, are particularly vulnerable to scabies and its secondary complications. Therefore, this study aimed to determine an appropriate ivermectin dose for children aged 2 to 4 years and weighing ≤15 kg. We conducted a prospective, pharmacokinetic study of ivermectin in Indigenous Australian children aged between 5 and 15 years and weighing >15 kg. Doses of 200 μg/kg rounded to the nearest whole or half 3 mg tablet were given to children with scabies and ivermectin concentrations determined at two time points after dosing. A population pharmacokinetic model was developed using non-linear mixed effects modelling. A separate covariate database of children aged 2 to 4 years and weighing <15 kg was used to generate 1000 virtual patients and simulate the dose required to achieve equivalent drug exposure in young children as those aged ≥5 years. Overall, 26 children who had 48 ivermectin concentrations determined were included, 11 (42%) were male, the median age was 10.9 years and median body weight 37.6 kg. The final model was a two-compartment model with first-order absorption and linear elimination. For simulated children aged 2 to 4 years, a dose of 3 mg in children weighing 10-15 kg produced similar drug exposures to those >5 years. The median simulated area under the concentration-time curve was 976 μg∙h/L. Using modelling, we have identified a dosing strategy for ivermectin in children aged 2 to 4 years and weighing less than 15 kg that can be prospectively evaluated for safety and efficacy. |
format |
Article in Journal/Newspaper |
author |
Amanda Gwee Stephen Duffull Xiao Zhu Steven Y C Tong Noel Cranswick Brett McWhinney Jacobus Ungerer Joshua Francis Andrew C Steer |
author_facet |
Amanda Gwee Stephen Duffull Xiao Zhu Steven Y C Tong Noel Cranswick Brett McWhinney Jacobus Ungerer Joshua Francis Andrew C Steer |
author_sort |
Amanda Gwee |
title |
Population pharmacokinetics of ivermectin for the treatment of scabies in Indigenous Australian children. |
title_short |
Population pharmacokinetics of ivermectin for the treatment of scabies in Indigenous Australian children. |
title_full |
Population pharmacokinetics of ivermectin for the treatment of scabies in Indigenous Australian children. |
title_fullStr |
Population pharmacokinetics of ivermectin for the treatment of scabies in Indigenous Australian children. |
title_full_unstemmed |
Population pharmacokinetics of ivermectin for the treatment of scabies in Indigenous Australian children. |
title_sort |
population pharmacokinetics of ivermectin for the treatment of scabies in indigenous australian children. |
publisher |
Public Library of Science (PLoS) |
publishDate |
2020 |
url |
https://doi.org/10.1371/journal.pntd.0008886 https://doaj.org/article/e2c4720eb4d2415a8b78655c4b9e07b8 |
geographic |
Arctic |
geographic_facet |
Arctic |
genre |
Arctic |
genre_facet |
Arctic |
op_source |
PLoS Neglected Tropical Diseases, Vol 14, Iss 12, p e0008886 (2020) |
op_relation |
https://doi.org/10.1371/journal.pntd.0008886 https://doaj.org/toc/1935-2727 https://doaj.org/toc/1935-2735 1935-2727 1935-2735 doi:10.1371/journal.pntd.0008886 https://doaj.org/article/e2c4720eb4d2415a8b78655c4b9e07b8 |
op_doi |
https://doi.org/10.1371/journal.pntd.0008886 |
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PLOS Neglected Tropical Diseases |
container_volume |
14 |
container_issue |
12 |
container_start_page |
e0008886 |
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1766346078746050560 |