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Antivir Ther . Pharmacokinetics of zanamivir in critically ill patients undergoing continuous venovenous hemofiltration

tetano

Editor, Senior Moderator
Antivir Ther


. 2023 Feb;28(1):13596535221150746.
doi: 10.1177/13596535221150746.
Pharmacokinetics of zanamivir in critically ill patients undergoing continuous venovenous hemofiltration


André Wieringa[SUP] 1 2 [/SUP], Peter Gj Ter Horst[SUP] 1 [/SUP], GertJan Hj Wagenvoort[SUP] 3 [/SUP], Birgit Cp Koch[SUP] 2 4 [/SUP], Jasper J Haringman[SUP] 1 [/SUP]



Affiliations
Free article

Abstract

Background: Limited data exist for dosing of zanamivir in the setting of CVVH in the intensive care unit (ICU). Our objective is to report the pharmacokinetics and sieving coefficient (S[SUB]v[/SUB]) of zanamivir in patients receiving continuous venovenous hemofiltration (CVVH).
Methods: In this prospective observational study, patients of ≥18 years admitted to the ICU with a life-threatening Influenza A or B infection, treated with zanamivir i.v. undergoing CVVH were included. Patients received a zanamivir loading dose of 600 mg i.v., 12 h later followed by maintenance dosages two times daily according to the treating physician. Per patient, nine CFT plasma and nine ultrafiltrate samples were drawn on day 2 of treatment and analysed with a validated HPLC-MS/MS method.
Results: Four patients were included in the study. The zanamivir elimination half-life was prolonged with 5.6-9.9 h, compared to patients with normal renal function. A S[SUB]v[/SUB] of approximately 1.0 was identified, with unrestricted transport of zanamivir to the ultrafiltrate.
Conclusions: Zanamivir is well cleared by CVVH. In absence of the possibility for therapeutic drug monitoring, the ultrafiltration rate seems as a good surrogate parameter to estimate the CL[SUB]CVVH[/SUB] and may help guide the dosing of zanamivir.

Keywords: CRRT; ICU; antiviral therapy; influenza; neuraminidase inhibitor; pharmacokinetics; sieving coefficient; zanamivir.
 
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