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

Research output: Contribution to journalArticlepeer-review

2 Downloads (Pure)

Abstract

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.

Original languageEnglish
Article numbere0008886
Pages (from-to)1-10
Number of pages11
JournalPLoS Neglected Tropical Diseases
Volume14
Issue number12
DOIs
Publication statusPublished - 7 Dec 2020

Fingerprint

Dive into the research topics of 'Population pharmacokinetics of ivermectin for the treatment of scabies in Indigenous Australian children'. Together they form a unique fingerprint.

Cite this