Pharmacokinetics and Pharmacodynamics of Oseltamivir in Neonates, Infants and Children

Joseph   F.   Standing; Maria      Tsolia; Irja      Lutsar

doi:10.2174/18715265112129990003

Abstract

Pharmacokinetic-pharmacodynamic (PKPD) studies have the potential to yield useful information on whether and how a drug works, and what dose to use. This approach is often best suited to situations where dose-response relationships need to be elucidated and where randomisation is not feasible. Children make up around one third of cases during influenza outbreaks, and are more susceptible to certain complications such as otitis media. Despite this, high-quality randomised controlled trials (RCT) of antiviral therapies such as oseltamivir have not been performed, leaving open the question of whether and at what dose to use. This review therefore focusses on the available PKPD data in children. Oseltamivir has complex PK which requires modelling to properly understand the relationship between dose and concentration with time, and there is a lack of clarity on appropriate pharmacodynamic endpoints. Following a general overview of oseltamivir PKPD, this review seeks to summarise the available paediatric PKPD data, identify gaps in our knowledge and priorities for future research.

Keywords: Children, influenza, neuraminidase inhibitors, oseltamivir, pharmacodynamics, pharmacokinetics.