Population Pharmacokinetic/Pharmacodynamic Analysis of Intravenous Zanamivir in Healthy Adults and Hospitalized Adult and Pediatric Subjects With Influenza

Clin Transl Sci. 2020 Jan;13(1):157-168. doi: 10.1111/cts.12697. Epub 2019 Nov 7.

Abstract

Zanamivir is a potent and highly selective inhibitor of influenza neuraminidase in which the inhibition of this enzyme prevents the virus from infecting other cells and specifically prevents release of the new virion from the host cell membrane. It is available as an oral powder for inhalation and intravenous formulations. The current population pharmacokinetic model based on data from eight studies of subjects treated with the intravenous formulation (125 healthy adults and 533 hospitalized adult and pediatric subjects with suspected or confirmed influenza) suggested a decreased zanamivir clearance in pediatric and renal impairment adult subjects. It also indicates that b.i.d. dosing is necessary to keep the exposure in influenza infected subjects above the 90% inhibitory concentration values of recently circulating viruses over the dosing interval. In the exposure-response analysis (phases II and III studies), no apparent relationship was found between zanamivir exposure and clinically relevant pharmacodynamic end points.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Intravenous
  • Adolescent
  • Adult
  • Age Factors
  • Aged
  • Aged, 80 and over
  • Antiviral Agents / administration & dosage
  • Antiviral Agents / pharmacokinetics*
  • Child
  • Child, Preschool
  • Clinical Trials, Phase II as Topic
  • Clinical Trials, Phase III as Topic
  • Datasets as Topic
  • Dose-Response Relationship, Drug
  • Drug Administration Schedule
  • Female
  • Glomerular Filtration Rate
  • Healthy Volunteers
  • Hospitalization
  • Humans
  • Infant
  • Influenza A virus / isolation & purification
  • Influenza, Human / blood
  • Influenza, Human / drug therapy*
  • Influenza, Human / virology
  • Male
  • Middle Aged
  • Models, Biological
  • Multicenter Studies as Topic
  • Neuraminidase / antagonists & inhibitors
  • Renal Elimination
  • Time Factors
  • United States
  • Viral Load / drug effects
  • Young Adult
  • Zanamivir / administration & dosage
  • Zanamivir / pharmacokinetics*

Substances

  • Antiviral Agents
  • Neuraminidase
  • Zanamivir