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Clin Pharmacol Ther. 2019 Apr 16. doi: 10.1002/cpt.1456. [Epub ahead of print]

Ivermectin Dosing Strategy to Achieve Equivalent Exposure Coverage in Children and Adults.

Brussee JM1,2,3, Schulz JD1,2, Coulibaly JT1,2,4,5, Keiser J1,2, Pfister M2,3,6.

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Department of Medical Parasitology and Infection Biology, Swiss Tropical and Public Health Institute, Basel, Switzerland.
University of Basel, Basel, Switzerland.
Pediatric Pharmacology and Pharmacometrics, University Children's Hospital Basel (UKBB), University of Basel, Basel, Switzerland.
Unité de Formation et de Recherche Biosciences, Université Félix Houphouët-Boigny, Abidjan, Côte d'Ivoire.
Centre Suisse de Recherches Scientifiques en Côte d'Ivoire, Abidjan, Côte d'Ivoire.
Certara LP, Princeton, New Jersey, USA.


Ivermectin is a commonly used broad-spectrum antiparasitic drug, yet doses that produce consistent exposure coverage across age have not been characterized, and no data are available in children weighing < 15 kg. First, a population pharmacokinetic model is developed based on data from 200 children and 11 adults, treated with 100-600 μg/kg ivermectin. Second, model-based simulations are performed to identify a dosing strategy that achieves equivalent exposure coverage in children and adults. Median (90% confidence interval) clearance of 0.346 (0.12-0.73) L/hour/kg in pre-school-aged (2-5 years) children is similar to 0.352 (0.17-0.69) L/hour/kg in school-aged (6-12 years) children but higher than in adults (0.199 (0.10-0.31) L/hour/kg), resulting in significantly lower exposure in children following a 200 μg/kg dose. Simulations indicate that a dose increase to 300 and 250 μg/kg in children aged 2-5 and 6-12 years, respectively, will achieve equivalent ivermectin exposure coverage in children and adults.


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