Zanamivir exposure in healthy rats and rats with acute lung injury

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61388963%3A_____%2F25%3A00637801" target="_blank" >RIV/61388963:_____/25:00637801 - isvavai.cz</a>

Alternative codes found

RIV/00216208:11110/25:10500139 RIV/00064165:_____/25:10500139

Result on the web

<a href="https://doi.org/10.1080/07853890.2025.2534523" target="_blank" >https://doi.org/10.1080/07853890.2025.2534523</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1080/07853890.2025.2534523" target="_blank" >10.1080/07853890.2025.2534523</a>

Result language

angličtina

Original language name

Zanamivir exposure in healthy rats and rats with acute lung injury

Original language description

Objectives: The aim of this study was to evaluate the pharmacokinetics and lung penetration of zanamivir in healthy rats and rats with lipopolysaccharide (LPS)-induced acute lung injury (ALI). Materials and methods: Three pharmacokinetic (PK) studies have been conducted to evaluate systemic PK and local exposure of zanamivir in male Wistar rats (n = 62, 16 weeks old). Zanamivir was administered to healthy rats and rats with LPS-induced ALI intravenously (IV) and by inhalation (INH) via nebulisation. Serum and bronchoalveolar lavage (BAL) fluid concentrations were analysed to assess drug permeation across barriers. All zanamivir concentrations were determined using the HPLC-MS/MS method. Results: The concentrations of zanamivir in BAL after IV dosing were approximately 3.1-, 4.0- and 5.0-fold higher in healthy animals compared with ALI at 30, 60 and 240 min after dosing, respectively (p = 0.005, 0.001 and 0.016). Zanamivir permeation between BAL fluid and serum was compared for IV and INH administrations, revealing that the BAL AUC30-240 following IV administration was 6.5-fold lower than after INH. Furthermore, the AUC30-240 in BAL fluid after IV administration was approximately 3.3 times higher in healthy animals than those with ALI (35,815 vs. 10,886 ng/mL x h). ALI also reduced the rate and extent of systemic absorption compared to healthy conditions. The absolute bioavailability of nebulised zanamivir was 1.91%. Conclusions: Our findings confirm PK superiority of INH administration to achieve local intrapulmonary exposition and indicate that ALI significantly impairs zanamivir penetration into the lungs from systemic circulation.

Czech name

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Czech description

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Type

J_imp - Article in a specialist periodical, which is included in the Web of Science database

CEP classification

—

OECD FORD branch

10608 - Biochemistry and molecular biology

Project

—

Continuities

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Publication year

2025

Confidentiality

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Name of the periodical

Annals of Medicine

ISSN

0785-3890

e-ISSN

1365-2060

Volume of the periodical

57

Issue of the periodical within the volume

1

Country of publishing house

GB - UNITED KINGDOM

Number of pages

12

Pages from-to

2534523

UT code for WoS article

001531336000001

EID of the result in the Scopus database

2-s2.0-105011050613