Tweet
Clin Transl Sci. 2019 Oct 30. doi: 10.1111/cts.12697. [Epub ahead of print] Population Pharmacokinetic/Pharmacodynamic Analysis of Intravenous Zanamivir in Healthy Adults and Hospitalized Adult and Pediatric Subjects with Influenza.
Zuo P1,2, Collins J1,3, Okour M4, Barth A4, Shortino D1,5, Yates P6, Roberts G4, Watson HA6, Peppercorn A4, Hossain M4.
Author information
1 PAREXEL International, USA. 2 Current affiliation Astellas Pharma, Inc, USA. 3 Current affiliation GlaxoSmithKline, USA. 4 GlaxoSmithKline, USA. 5 Current affiliation Urovant Sciences. 6 GlaxoSmithKline, UK.
Abstract
Zanamivir is a potent and highly selective inhibitor of influenza neuraminidase where 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 tintravenous 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 twice daily dosing is necessary to keep the exposure in influenza infected subjects above the IC90 values of recently circulating viruses over the dosing interval. In the exposure-response analysis (Phase II and III study), no apparent relationship was found between zanamivir exposure and clinically relevant pharmacodynamic endpoints.
? 2019 The Authors. Clinical and Translational Science published by Wiley Periodicals, Inc. on behalf of the American Society for Clinical Pharmacology and Therapeutics.
KEYWORDS:
Exposure-Response; Influenza Infection; Pediatrics; Population Pharmacokinetics
PMID: 31664778 DOI: 10.1111/cts.12697