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- Title
Population pharmacokinetics of ivermectin for the treatment of scabies in Indigenous Australian children.
- Authors
Gwee, Amanda; Duffull, Stephen; Zhu, Xiao; Tong, Steven Y. C.; Cranswick, Noel; McWhinney, Brett; Ungerer, Jacobus; Francis, Joshua; Steer, Andrew C.
- 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. Author summary: Ivermectin is an important drug for the control and treatment of neglected tropical diseases. However, despite numerous studies showing that ivermectin is safe and well tolerated in young children, it is not currently recommended in young children <5 years and <15 kg. Therefore, there are no guidelines for the dose of ivermectin in young or small children. In this study, we firstly determined how much ivermectin is present in blood in children aged 5 years and older. We then used this information to model what happens to ivermectin in the body of children allowing us to calculate the dose required in children aged less than 5 years and weighing under 15 kg. This study provides a new dosing guideline that can now be tested in clinical studies of children <5 years and <15 kg.
- Subjects
AUSTRALIA; INDIGENOUS children; INDIGENOUS Australians; IVERMECTIN; AUSTRALIANS; PHARMACOKINETICS; JUNK food
- Publication
PLoS Neglected Tropical Diseases, 2020, Vol 14, Issue 12, p1
- ISSN
1935-2727
- Publication type
Article
- DOI
10.1371/journal.pntd.0008886