Abstract
Objective
The prodrug oseltamivir has been shown to be efficacious and safe for the treatment of influenza for patients 1 year of age or older; however, pharmacokinetic information was lacking for children below 5 years of age. This study was conducted to assess the metabolic and excretory capacity of oseltamivir and its active carboxylate metabolite in young children.
Methods
Twelve healthy children aged 1–5 years received a single oral suspension dose of oseltamivir (45 mg for 3–5 years, 30 mg for 1–2 years). Plasma and urine concentrations of oseltamivir and the carboxylate were determined by means of liquid chromatography/tandem mass spectrometry.
Results
Mean peak plasma concentration and area under the plasma concentration–time curve values normalized to milligram per kilogram oseltamivir dose in the 1- to 2-year group are lower than those in the 3- to 5-year group. Mean body weight normalized oral clearance of oseltamivir and its carboxylate in younger subjects aged 1–2 years (259 ml/min/kg and 12.2 ml/min/kg) were, respectively, 52% and 30% higher than those in older subjects aged 3–5 years (170 ml/min/kg and 9.4 ml/min/kg).
Conclusion
The results demonstrate that infants as young as 1 year old can metabolize and excrete oseltamivir efficiently. The data derived from this study provide the starting dose of oseltamivir for further investigation in an efficacy study among influenza-infected infants less than 1 year of age.
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Acknowledgement
The study was fully sponsored by F. Hoffmann-La Roche Ltd., Basel, Switzerland.
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Oo, C., Hill, G., Dorr, A. et al. Pharmacokinetics of anti-influenza prodrug oseltamivir in children aged 1–5 years. Eur J Clin Pharmacol 59, 411–415 (2003). https://doi.org/10.1007/s00228-003-0639-6
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DOI: https://doi.org/10.1007/s00228-003-0639-6