Oseltamivir pharmacology in young children: a commentary

Oseltamivir is listed by the World Health Organization as an essential drug for the treatment and prophylaxis of both seasonal and pandemic influenza. Since influenza mortality is highest in neonates and infants, optimal dosing of oseltamivir in this high risk population is of utmost public health concern. To date, only two major clinical trials have been conducted investigating oselatmivir exposure and exposure/response in neonates and infants. The first study was a prospective, open label pharmacokinetic/pharmacodynamic and safety evaluation of oseltamivir in a total of 87 young children less than 2 years of age and was conducted by the National Institute of Allergy and Infectious Diseases (NIAID) Collaborative Antiviral Study Group (CASG). The second Roche sponsored study was also an open label, prospective, pharmacokinetic/ pharmacodynamic and safety evaluation of oseltamivir in the treatment of 65 children less than 12 months of age. A recent supplemental new drug application (sNDA) was submitted to the Food and Drug Administration (FDA) on the basis of these two studies which resulted in oseltamivir becoming the first and so far only neuraminidase inhibitor to gain FDA approval for treatment of influenza in neonates and infants less than 1 year of age. The two review articles in this volume discuss the complex pharmacokinetics of oseltamivir and its active metabolite oseltamivir carboxylate from different perspectives while attempting to contrast and critique different literature views of the optimal dose in neonates, infants and young children. The articles also offer suggestions to generate more robust pediatric PKPD data and mend current gaps in knowledge.