Ivacaftor pharmacokinetics and lymphatic transport after enteral administration in rats

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00064165%3A_____%2F24%3A10478251" target="_blank" >RIV/00064165:_____/24:10478251 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/00216208:11110/24:10478251 RIV/00216208:11130/24:10478251 RIV/00216208:11310/24:10478251 RIV/00064203:_____/24:10478251

Výsledek na webu

<a href="https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=17WgQFTdo7" target="_blank" >https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=17WgQFTdo7</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.3389/fphar.2024.1331637" target="_blank" >10.3389/fphar.2024.1331637</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Ivacaftor pharmacokinetics and lymphatic transport after enteral administration in rats

Popis výsledku v původním jazyce

Background: Ivacaftor is a modern drug used in the treatment of cystic fibrosis. It is highly lipophilic and exhibits a strong positive food effect. These characteristics can be potentially connected to a pronounced lymphatic transport after oral administration. Methods: A series of studies was conducted to describe the basic pharmacokinetic parameters of ivacaftor in jugular vein cannulated rats when dosed in two distinct formulations: an aqueous suspension and an oil solution. Additionally, an anesthetized mesenteric lymph duct cannulated rat model was studied to precisely assess the extent of lymphatic transport. Results: Mean +- SD ivacaftor oral bioavailability was 18.4 +- 3.2% and 16.2 +- 7.8%, respectively, when administered as an aqueous suspension and an oil solution. The relative contribution of the lymphatic transport to the overall bioavailability was 5.91 +- 1.61% and 4.35 +- 1.84%, respectively. Conclusion: Lymphatic transport plays only a minor role in the process of ivacaftor intestinal absorption, and other factors are, therefore, responsible for its pronounced positive food effect.

Název v anglickém jazyce

Ivacaftor pharmacokinetics and lymphatic transport after enteral administration in rats

Popis výsledku anglicky

Background: Ivacaftor is a modern drug used in the treatment of cystic fibrosis. It is highly lipophilic and exhibits a strong positive food effect. These characteristics can be potentially connected to a pronounced lymphatic transport after oral administration. Methods: A series of studies was conducted to describe the basic pharmacokinetic parameters of ivacaftor in jugular vein cannulated rats when dosed in two distinct formulations: an aqueous suspension and an oil solution. Additionally, an anesthetized mesenteric lymph duct cannulated rat model was studied to precisely assess the extent of lymphatic transport. Results: Mean +- SD ivacaftor oral bioavailability was 18.4 +- 3.2% and 16.2 +- 7.8%, respectively, when administered as an aqueous suspension and an oil solution. The relative contribution of the lymphatic transport to the overall bioavailability was 5.91 +- 1.61% and 4.35 +- 1.84%, respectively. Conclusion: Lymphatic transport plays only a minor role in the process of ivacaftor intestinal absorption, and other factors are, therefore, responsible for its pronounced positive food effect.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

30104 - Pharmacology and pharmacy

Projekt

—

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2024

Kód důvěrnosti údajů

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

Název periodika

Frontiers in Pharmacology

ISSN

1663-9812

e-ISSN

1663-9812

Svazek periodika

15

Číslo periodika v rámci svazku

February

Stát vydavatele periodika

CH - Švýcarská konfederace

Počet stran výsledku

8

Strana od-do

1331637

Kód UT WoS článku

001175811600001

EID výsledku v databázi Scopus

2-s2.0-85186616289