title: Pharmacokinetics and pharmacodynamics of oseltamivir in neonates, infants and children.
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.
authors.affiliation: Infectious Diseases and Microbiology Unit, University College London, Institute of Child Health, London, WC1N 1EH, UK. j.standing@ucl.ac.uk
authors.forename: Joseph F
authors.initials: JF
authors.lastname: Standing
authors.forename: Maria
authors.initials: M
authors.lastname: Tsolia
authors.forename: Irja
authors.initials: I
authors.lastname: Lutsar
mesh_terms: D000998:Antiviral Agents / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*; D002648:Child; D002675:Child, Preschool; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007251:Influenza, Human / Q000188:drug therapy*; D008954:Models, Biological; D009439:Neuraminidase / Q000037:antagonists & inhibitors*; D053139:Oseltamivir / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*; D014764:Viral Proteins / Q000037:antagonists & inhibitors*
chemical_list: D000998:Antiviral Agents; D004791:Enzyme Inhibitors; D014764:Viral Proteins; D053139:Oseltamivir; D009439:Neuraminidase