Oseltamivir pharmacokinetics and clinical experience in neonates and infants during an outbreak of H1N1 influenza A virus infection in a neonatal intensive care unit

Antimicrob Agents Chemother. 2012 Jul;56(7):3833-40. doi: 10.1128/AAC.00290-12. Epub 2012 May 7.

Abstract

Detailed oseltamivir pharmacokinetics have yet to be reported in neonates and infants; this group is at high risk of serious influenza-associated complications. Extrapolation of doses from older patients is complicated by rapid organ and drug-metabolizing enzyme maturation. A pharmacokinetic study has been conducted during an influenza A(H1N1) outbreak in a neonatal intensive care unit. Each included patient provided 4 samples for oseltamivir and 4 samples for its active metabolite oseltamivir carboxylate. A population pharmacokinetic model was developed with NONMEM. Allometric weight scaling and maturation functions were added a priori to scale for size and age based on literature values. Nine neonates and infants were recruited. A physiologically parameterized pharmacokinetic model predicted typical day 1 area under the curve (AUC(0-12)) values of 1,966 and 2,484 μg · h/liter for neonates and infants of ≤ 37 weeks of postmenstrual age (PMA) and >37 weeks of PMA treated with 1 mg/kg of body weight and 2 mg/kg, respectively. The corresponding steady-state AUC(0-12) values were 3,670 and 4,559 μg · h/liter. Premature neonates treated with 1 mg/kg and term babies treated with 2 mg/kg should have average oseltamivir carboxylate concentrations in a range similar to that for adults treated with 75 mg, corresponding to >200-fold above the half-maximal inhibitory concentration (IC(50)) value for influenza A(H1N1) from the start of therapy.

Publication types

  • Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antiviral Agents / pharmacokinetics*
  • Antiviral Agents / therapeutic use*
  • Disease Outbreaks
  • Female
  • Humans
  • Infant, Newborn
  • Influenza A Virus, H1N1 Subtype / drug effects
  • Influenza A Virus, H1N1 Subtype / pathogenicity*
  • Influenza, Human / drug therapy*
  • Intensive Care Units
  • Male
  • Oseltamivir / pharmacokinetics*
  • Oseltamivir / therapeutic use*

Substances

  • Antiviral Agents
  • Oseltamivir