Zanamivir exposure in healthy rats and rats with acute lung injury

Kód výsledku v 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>

Nalezeny alternativní kódy

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

Výsledek na webu

<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>

Jazyk výsledku

angličtina

Název v původním jazyce

Zanamivir exposure in healthy rats and rats with acute lung injury

Popis výsledku v původním jazyce

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.

Název v anglickém jazyce

Zanamivir exposure in healthy rats and rats with acute lung injury

Popis výsledku anglicky

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.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

10608 - Biochemistry and molecular biology

Projekt

—

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2025

Kód důvěrnosti údajů

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

Název periodika

Annals of Medicine

ISSN

0785-3890

e-ISSN

1365-2060

Svazek periodika

57

Číslo periodika v rámci svazku

1

Stát vydavatele periodika

GB - Spojené království Velké Británie a Severního Irska

Počet stran výsledku

12

Strana od-do

2534523

Kód UT WoS článku

001531336000001

EID výsledku v databázi Scopus

2-s2.0-105011050613