Open AccessPopulation Pharmacokinetic/Pharmacodynamic Analysis of Intravenous Zanamivir in Healthy Adults and Hospitalized Adult and Pediatric Subjects With Influenza
Author(s) -
Zuo Peiying,
Collins Jon,
Okour Malek,
Barth Aline,
Shortino Denise,
Yates Phillip,
Roberts Grace,
Watson Helen A.,
Peppercorn Amanda,
Hossain Mohammad
Publication year - 2020
Publication title -
clinical and translational science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.303
H-Index - 44
eISSN - 1752-8062
pISSN - 1752-8054
DOI - 10.1111/cts.12697
Subject(s) - zanamivir , neuraminidase inhibitor , dosing , pharmacodynamics , medicine , pharmacokinetics , population , neuraminidase , pharmacology , oseltamivir , virus , immunology , covid-19 , disease , environmental health , infectious disease (medical specialty)
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.