Population pharmacokinetics of ivermectin for the treatment of scabies in Indigenous Australian children

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.

A Large Impact of Obesity on the Disposition of Ivermectin, Moxidectin and Eprinomectin in a Canine Model: Relevance for COVID-19 Patients

“…Recommendation of a weight-based oral dosage of IVM assumes that plasma clearance is directly proportional to Total Body Weight (TBW), regardless of body composition. This is supported by several population pharmacokinetic investigations, which have shown that body weight is the relevant covariate (Schulz et al, 2019;Gwee et al, 2020). In a small, homogeneous trial, which enrolled 12 healthy volunteers, only BW was a significant covariate for plasma clearance and volume of distribution, while the Body Mass Index (from 18.1 to 26.4 kg/square meter) was not significant (Duthaler et al, 2019).…”

Scabies in Koranic schools in Dakar, Senegal: Comparison of two therapeutic modalities

“…This strategy has shown its effectiveness in koranic schools in Bangladesh. The best results with ivermectin have been obtained in trials carried out on islands -poorer results, including Australia, have been seen in land-based or city settings (Gwee et al, 2020).…”

The Current Directions of Searching for Antiparasitic Drugs

“…It is effective in onchocerciasis; the disease caused by the Loa loa nematode and in lymphatic filariasis [ 32 ]. It is used to treat and control soil-transmitted helminths, strongyloidiasis [ 33 ]. In Australia, the substance is also approved for the treatment of scabies.…”