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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.

Author information

1
Department of Medical Parasitology and Infection Biology, Swiss Tropical and Public Health Institute, Basel, Switzerland.
2
University of Basel, Basel, Switzerland.
3
Pediatric Pharmacology and Pharmacometrics, University Children's Hospital Basel (UKBB), University of Basel, Basel, Switzerland.
4
Unité de Formation et de Recherche Biosciences, Université Félix Houphouët-Boigny, Abidjan, Côte d'Ivoire.
5
Centre Suisse de Recherches Scientifiques en Côte d'Ivoire, Abidjan, Côte d'Ivoire.
6
Certara LP, Princeton, New Jersey, USA.

Abstract

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.

PMID:
30993667
DOI:
10.1002/cpt.1456

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