Pharmacokinetics of anti-influenza prodrug oseltamivir in children aged 1-5 years.
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).


CONCLUSIONS
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.
Oo
Charles
C
Roche Global Development, Nutley, NJ, USA. charles.oo@aventis.com
Hill
George
G
Dorr
Albert
A
Liu
Baolian
B
Boellner
Samuel
S
Ward
Penelope
P
D000081:Acetamides / Q000008:administration & dosage / Q000493:pharmacokinetics*; D000284:Administration, Oral; D000367:Age Factors; D000998:Antiviral Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D019540:Area Under Curve; D002675:Child, Preschool; D005260:Female; D006207:Half-Life; D006801:Humans; D007223:Infant; D007251:Influenza, Human / Q000188:drug therapy; D008297:Male; D009439:Neuraminidase / Q000037:antagonists & inhibitors*; D053139:Oseltamivir; D011355:Prodrugs / Q000008:administration & dosage / Q000493:pharmacokinetics*
D000081:Acetamides; D000998:Antiviral Agents; D011355:Prodrugs; D053139:Oseltamivir; D009439:Neuraminidase