Prolonged release pirfenidone pharmacokinetics is modified in cirrhosis GENESIS study

Prolonged release pirfenidone pharmacokinetics is modified in cirrhosis GENESIS study

In both clinical and experimental trials, pirfenidone (PFD) showed anti-inflammatory and antifibrogenic effects. Considering the wide variation in hepatic functional reserve in patients with cirrhosis, we decided to learn more about the pharmacokinetics of a new formulation of prolonged release PFD...

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Bibliographic Details
Published in:Biomedicine & pharmacotherapy Vol. 168; p. 115712
Main Authors: Poo, Jorge L., Aguilar, Juan R., Bernal-Reyes, Raul, Alonso-Campero, Rosalba, Gasca, Frida, Hernández, Larissa, Pineyro-Garza, Everardo, Gomez-Silva, Magdalena, Gamino, Maria Elena, la Parra, Mario González-de, Peña, Pedro, Hernández, Nadiel, Tapia, Graciela, Muñoz-Espinosa, Linda E.
Format: Journal Article
Language:English
Published: Elsevier Masson SAS 01-12-2023
Subjects:
Antifibrotic
Child-Pugh A and B cirrhosis
Liver fibrosis
Pharmacokinetics
Prolonged-release pirfenidone
Prolonged-release pirfenidone
Antifibrotic
LLOQ
FDA
Child-Pugh A and B cirrhosis
MS
IS
Liver fibrosis
INR
AUC
ALD
HCV
Pharmacokinetics
IPF
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Summary:In both clinical and experimental trials, pirfenidone (PFD) showed anti-inflammatory and antifibrogenic effects. Considering the wide variation in hepatic functional reserve in patients with cirrhosis, we decided to learn more about the pharmacokinetics of a new formulation of prolonged release PFD in this population (PR-PFD), focusing on assessing changes on AUC0–∞, AUC0–t, and Cmax. In this study, 24 subjects with cirrhosis were included: eight subjects with mild liver impairment (Child–Pugh A) and eight with moderate liver impairment (Child–Pugh B), and a third group of eight age-matched subjects without fibrosis. All participants were under fasting conditions before receiving orally two 600-mg tablets of a prolonged-release formulation of pirfenidone (PR-PFD) and remained in the clinical unit for 36 h after PR-PFD administration. Serial blood samples were collected after dosing (0.5-36 h). A validated high-performance liquid chromatography–mass spectrometry method was used to determine PFD plasma concentrations. The exposure to PR-PFD was 3.6- and 4.4-fold greater in subjects with Child–Pugh A and Child–Pugh B than in subjects without cirrhosis, and Cmax was 1.6- and 1.8-fold greater in subjects with Child–Pugh B and Child–Pugh-A than in patients without cirrhosis, without significant differences between the two cirrhotic groups. PFD was well tolerated. The pharmacokinetic parameters of PR-PFD are significantly modified in patients with cirrhosis compared with those in controls, indicating that liver impairment should be considered in clinical practice. [Display omitted]
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ISSN:0753-3322
1950-6007
DOI:10.1016/j.biopha.2023.115712