Oseltamivir pharmacokinetics, dosing, and resistance among children aged <2 years with influenza.

Abstract

BACKGROUND:

Children <2 years of age are at high risk of influenza-related mortality and morbidity. However, the appropriate dose of oseltamivir for children <2 years of age is unknown.

METHODS:

The National Institute of Allergy and Infectious Diseases Collaborative Antiviral Study Group evaluated oseltamivir in infants aged <2 years in an age-de-escalation, adaptive design with a targeted systemic exposure.

RESULTS:

From 2006 to 2010, 87 subjects enrolled. An oseltamivir dose of 3.0 mg/kg produced drug exposures within the target range in subjects 0-8 months of age, although there was a greater degree of variability in infants <3 months of age. In subjects 9-11 months of age, a dose of 3.5 mg/kg produced drug exposures within the target range. Six of 10 subjects aged 12-23 months receiving the Food and Drug Administration-approved unit dose for this age group (ie, 30 mg) had oseltamivir carboxylate exposures below the target range. Virus from 3 subjects developed oseltamivir resistance during antiviral treatment.

CONCLUSIONS:

The appropriate twice-daily oral oseltamivir dose for infants ≤8 months of age is 3.0 mg/kg, while the dose for infants 9-11 months old is 3.5 mg/kg.

• Authors: David W Kimberlin, Edward P Acosta, Mark N Prichard, Pablo J Sánchez, Krow Ampofo, David Lang, Negar Ashouri, John A Vanchiere, Mark J Abzug, Nazha Abughali, Mary T Caserta, Janet A Englund, Sunil K Sood, Michael G Spigarelli, John S Bradley, Judy Lew, Marian G Michaels, Wen Wan, Gretchen Cloud, Penelope Jester, Fred D Lakeman, Richard J Whitley, National Institute of Allergy and Infectious Diseases Collaborative Antiviral Study Group
• Journal: The Journal of infectious diseases (J Infect Dis) Vol. 207 Issue 5 Pg. 709-20 (Mar 01 2013) ISSN: 1537-6613 [Electronic] United States
• PMID: 23230059 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)

Chemical References

• Oseltamivir

Topics

• Administration, Oral
• Drug Resistance, Viral
• Female
• Humans
• Infant
• Infant, Newborn
• Influenza, Human (drug therapy, virology)
• Male
• Orthomyxoviridae (drug effects, isolation & purification)
• Oseltamivir (administration & dosage, pharmacokinetics, pharmacology)