Pharmacokinetics and dosage recommendations for an oseltamivir oral suspension for the treatment of influenza in children.
OBJECTIVE
Oseltamivir (Ro 64-0796) is an ester prodrug of the active metabolite Ro 64-0802 (oseltamivir carboxylate), a potent and selective inhibitor of the neuraminidase enzyme of influenza virus. In this study we report the pharmacokinetics of oseltamivir in healthy children volunteers (study 1) and in children with influenza (study 2).


METHODS
In study 1, an open-label, single dose study, serial plasma samples were obtained from a total of 18 healthy children (5 to 18 years) who were grouped by age (n = 6 per group) and received single oral doses of oseltamivir 2 mg/kg. In study 2, a randomised, placebo controlled phase III study in paediatric children (1 to 12 years) presenting with influenza symptoms, 199 pharmacokinetic sparse samples were obtained from 87 patients, and serial samples were obtained from 5 patients. Pooled data were compared with those from adult studies.


RESULTS
Children (1 to 12 years) eliminated the active metabolite faster than both adolescents (13 to 18 years) and adults, resulting in lower exposure to the active drug. In these children, oseltamivir 2 mg/kg twice daily resulted in drug exposures within the range associated with tolerability and efficacy in adults administered approximately 1 mg/kg twice daily. Unit doses of oseltamivir 30, 45 and 60mg oral suspension are recommended twice daily in children weighing < or =15 kg (or < or =33 lb, aged 1 to 3 years), > 15 to 23 kg (or >33 to 51 lb, aged 4 to 7 years) and >23 to 40 kg (or >51 to 88 lb, aged 8 to 12 years), respectively. A 75 mg capsule may be a viable dosage formulation in children (e.g. over 8 years of age) who are able to swallow solid dosage forms.


CONCLUSIONS
Young children cleared the active metabolite oseltamivir carboxylate at a faster rate than older children and adults. Convenient administration recommendations for the oseltamivir oral suspension in children are possible to maintain drug exposure within the target window.
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Department of Clinical Pharmacology, Roche Global Development, Nutley, New Jersey 07110, USA. charles.oo@roche.com
Barrett
J
J
Hill
G
G
Mann
J
J
Dorr
A
A
Dutkowski
R
R
Ward
P
P
D000081:Acetamides / Q000008:administration & dosage / Q000378:metabolism / Q000493:pharmacokinetics* / Q000627:therapeutic use; D000284:Administration, Oral; D000293:Adolescent; D000998:Antiviral Agents / Q000008:administration & dosage / Q000378:metabolism / Q000493:pharmacokinetics* / Q000627:therapeutic use; D019540:Area Under Curve; D002648:Child; D002675:Child, Preschool; D004311:Double-Blind Method; D004791:Enzyme Inhibitors / Q000627:therapeutic use; D005260:Female; D006207:Half-Life; D006801:Humans; D007223:Infant; D009980:Influenza A virus / Q000187:drug effects; D009981:Influenza B virus / Q000187:drug effects; D007251:Influenza, Human / Q000188:drug therapy* / Q000821:virology; D008297:Male; D009439:Neuraminidase / Q000037:antagonists & inhibitors; D053139:Oseltamivir
D000081:Acetamides; D000998:Antiviral Agents; D004791:Enzyme Inhibitors; D053139:Oseltamivir; D009439:Neuraminidase