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

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.

• Authors: Joseph F Standing, Angela Nika, Vasileios Tsagris, Ioannis Kapetanakis, Helena C Maltezou, Dimitris A Kafetzis, Maria N Tsolia
• Journal: Antimicrobial agents and chemotherapy (Antimicrob Agents Chemother) Vol. 56 Issue 7 Pg. 3833-40 (Jul 2012) ISSN: 1098-6596 [Electronic] United States
• PMID: 22564835 (Publication Type: Clinical Trial, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antiviral Agents
• Oseltamivir

Topics

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