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

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 JesterFred D. Lakeman, Richard J. Whitley, Dusty Giles, Bari Cotton, Sharon Judy, Margaret Cowie, Jeanne Francis, Candice Evans, Nan O'donnell, Ofelia Vargas Shiraishi, Lisa Latiolais, Valeri Aymami, Ken Dole, Julie Gaultier, Gerry Lofthus, Diane Kinnunen, Kirsten Lacombe, Nancy Stellato, Julie Denlinger, Sara Hingtgen, Christina Mason, Noreen Jeffrey

Research output: Contribution to journalArticle

35 Citations (Scopus)

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.Clinical Trials Registration. NCT00391768.

Original languageEnglish (US)
Pages (from-to)709-720
Number of pages12
JournalJournal of Infectious Diseases
Volume207
Issue number5
DOIs
StatePublished - Mar 1 2013

Fingerprint

Oseltamivir
Human Influenza
Pharmacokinetics
Antiviral Agents
National Institute of Allergy and Infectious Diseases (U.S.)
United States Food and Drug Administration
Pharmaceutical Preparations
Age Groups
Clinical Trials
Viruses
Morbidity
Mortality

Keywords

  • antiviral resistance
  • antiviral treatment
  • influenza
  • Oseltamivir
  • Tamiflu

ASJC Scopus subject areas

  • Infectious Diseases
  • Immunology and Allergy

Cite this

Kimberlin, D. W., Acosta, E. P., Prichard, M. N., Sánchez, P. J., Ampofo, K., Lang, D., ... Jeffrey, N. (2013). Oseltamivir pharmacokinetics, dosing, and resistance among children aged <2 years with influenza. Journal of Infectious Diseases, 207(5), 709-720. https://doi.org/10.1093/infdis/jis765

Oseltamivir pharmacokinetics, dosing, and resistance among children aged <2 years with influenza. / Kimberlin, David W.; Acosta, Edward P.; Prichard, Mark N.; Sánchez, Pablo J.; Ampofo, Krow; Lang, David; Ashouri, Negar; Vanchiere, John A.; Abzug, Mark J.; Abughali, Nazha; Caserta, Mary T.; Englund, Janet A.; Sood, Sunil K.; Spigarelli, Michael G.; Bradley, John S.; Lew, Judy; Michaels, Marian G.; Wan, Wen; Cloud, Gretchen; Jester, Penelope; Lakeman, Fred D.; Whitley, Richard J.; Giles, Dusty; Cotton, Bari; Judy, Sharon; Cowie, Margaret; Francis, Jeanne; Evans, Candice; O'donnell, Nan; Shiraishi, Ofelia Vargas; Latiolais, Lisa; Aymami, Valeri; Dole, Ken; Gaultier, Julie; Lofthus, Gerry; Kinnunen, Diane; Lacombe, Kirsten; Stellato, Nancy; Denlinger, Julie; Hingtgen, Sara; Mason, Christina; Jeffrey, Noreen.

In: Journal of Infectious Diseases, Vol. 207, No. 5, 01.03.2013, p. 709-720.

Research output: Contribution to journalArticle

Kimberlin, DW, Acosta, EP, Prichard, MN, Sánchez, PJ, Ampofo, K, Lang, D, Ashouri, N, Vanchiere, JA, Abzug, MJ, Abughali, N, Caserta, MT, Englund, JA, Sood, SK, Spigarelli, MG, Bradley, JS, Lew, J, Michaels, MG, Wan, W, Cloud, G, Jester, P, Lakeman, FD, Whitley, RJ, Giles, D, Cotton, B, Judy, S, Cowie, M, Francis, J, Evans, C, O'donnell, N, Shiraishi, OV, Latiolais, L, Aymami, V, Dole, K, Gaultier, J, Lofthus, G, Kinnunen, D, Lacombe, K, Stellato, N, Denlinger, J, Hingtgen, S, Mason, C & Jeffrey, N 2013, 'Oseltamivir pharmacokinetics, dosing, and resistance among children aged <2 years with influenza', Journal of Infectious Diseases, vol. 207, no. 5, pp. 709-720. https://doi.org/10.1093/infdis/jis765
Kimberlin, David W. ; Acosta, Edward P. ; Prichard, Mark N. ; Sánchez, Pablo J. ; Ampofo, Krow ; Lang, David ; Ashouri, Negar ; Vanchiere, John A. ; Abzug, Mark J. ; Abughali, Nazha ; Caserta, Mary T. ; Englund, Janet A. ; Sood, Sunil K. ; Spigarelli, Michael G. ; Bradley, John S. ; Lew, Judy ; Michaels, Marian G. ; Wan, Wen ; Cloud, Gretchen ; Jester, Penelope ; Lakeman, Fred D. ; Whitley, Richard J. ; Giles, Dusty ; Cotton, Bari ; Judy, Sharon ; Cowie, Margaret ; Francis, Jeanne ; Evans, Candice ; O'donnell, Nan ; Shiraishi, Ofelia Vargas ; Latiolais, Lisa ; Aymami, Valeri ; Dole, Ken ; Gaultier, Julie ; Lofthus, Gerry ; Kinnunen, Diane ; Lacombe, Kirsten ; Stellato, Nancy ; Denlinger, Julie ; Hingtgen, Sara ; Mason, Christina ; Jeffrey, Noreen. / Oseltamivir pharmacokinetics, dosing, and resistance among children aged <2 years with influenza. In: Journal of Infectious Diseases. 2013 ; Vol. 207, No. 5. pp. 709-720.
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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.Clinical Trials Registration. NCT00391768.",
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T1 - Oseltamivir pharmacokinetics, dosing, and resistance among children aged <2 years with influenza

AU - Kimberlin, David W.

AU - Acosta, Edward P.

AU - Prichard, Mark N.

AU - Sánchez, Pablo J.

AU - Ampofo, Krow

AU - Lang, David

AU - Ashouri, Negar

AU - Vanchiere, John A.

AU - Abzug, Mark J.

AU - Abughali, Nazha

AU - Caserta, Mary T.

AU - Englund, Janet A.

AU - Sood, Sunil K.

AU - Spigarelli, Michael G.

AU - Bradley, John S.

AU - Lew, Judy

AU - Michaels, Marian G.

AU - Wan, Wen

AU - Cloud, Gretchen

AU - Jester, Penelope

AU - Lakeman, Fred D.

AU - Whitley, Richard J.

AU - Giles, Dusty

AU - Cotton, Bari

AU - Judy, Sharon

AU - Cowie, Margaret

AU - Francis, Jeanne

AU - Evans, Candice

AU - O'donnell, Nan

AU - Shiraishi, Ofelia Vargas

AU - Latiolais, Lisa

AU - Aymami, Valeri

AU - Dole, Ken

AU - Gaultier, Julie

AU - Lofthus, Gerry

AU - Kinnunen, Diane

AU - Lacombe, Kirsten

AU - Stellato, Nancy

AU - Denlinger, Julie

AU - Hingtgen, Sara

AU - Mason, Christina

AU - Jeffrey, Noreen

PY - 2013/3/1

Y1 - 2013/3/1

N2 - 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.Clinical Trials Registration. NCT00391768.

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KW - antiviral treatment

KW - influenza

KW - Oseltamivir

KW - Tamiflu

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