TY - JOUR
T1 - Pharmacokinetic evaluation of two pirfenidone formulations in patients with idiopathic pulmonary fibrosis and chronic hypersensitivity pneumonitis
AU - Barranco-Garduño, Lina Marcela
AU - Buendía-Roldan, Ivette
AU - Rodriguez, Juan Jose
AU - González-Ramírez, Rodrigo
AU - Cervantes-Nevárez, Ariadna N.
AU - Neri-Salvador, Juan Carlos
AU - Carrasco-Portugal, Miriam del Carmen
AU - Castañeda-Hernández, Gilberto
AU - Martinez-Espinosa, Karen
AU - Selman, Moisés
AU - Flores-Murrieta, Francisco Javier
N1 - Publisher Copyright:
© 2020 The Authors
PY - 2020/10
Y1 - 2020/10
N2 - Idiopathic pulmonary fibrosis (IPF) is a progressive and fatal disease characterized by an abnormal activation of lung epithelium and fibroblasts, as well as an excessive accumulation of extracellular matrix. Pirfenidone was introduced as a therapeutic option for IPF and chronic hypersensitive pneumonitis (cHP), a related disease. However, high plasma concentrations, which can be achieved even at recommended doses, are frequently associated with adverse events. Hence, an extended release formulation (XP), yielding lower peak plasma concentrations, has been developed. The aim of this study was to compare the pharmacokinetic properties of XP with those of the immediate (IR) formulation in patients with IPF or cHP. Data were analyzed using two pharmacokinetic approaches, conventional non compartmental analysis and a population analysis using the nonlinear mixed effects model technique. Results observed with both approaches were consistent. Drug exposure was similar with both formulations. However, XP exhibited less concentration fluctuations and a longer mean resident time. These results suggest that XP could be a feasible option to reduce adverse events associated to pirfenidone elevated concentrations. Nevertheless, efficacy studies are required to fully document the therapeutic potential of XP.
AB - Idiopathic pulmonary fibrosis (IPF) is a progressive and fatal disease characterized by an abnormal activation of lung epithelium and fibroblasts, as well as an excessive accumulation of extracellular matrix. Pirfenidone was introduced as a therapeutic option for IPF and chronic hypersensitive pneumonitis (cHP), a related disease. However, high plasma concentrations, which can be achieved even at recommended doses, are frequently associated with adverse events. Hence, an extended release formulation (XP), yielding lower peak plasma concentrations, has been developed. The aim of this study was to compare the pharmacokinetic properties of XP with those of the immediate (IR) formulation in patients with IPF or cHP. Data were analyzed using two pharmacokinetic approaches, conventional non compartmental analysis and a population analysis using the nonlinear mixed effects model technique. Results observed with both approaches were consistent. Drug exposure was similar with both formulations. However, XP exhibited less concentration fluctuations and a longer mean resident time. These results suggest that XP could be a feasible option to reduce adverse events associated to pirfenidone elevated concentrations. Nevertheless, efficacy studies are required to fully document the therapeutic potential of XP.
KW - Biological Sciences
KW - Health Sciences
KW - Internal Medicine
KW - Pharmaceutical science
KW - Pharmacology
KW - Pulmonary fibrosis
KW - Respiratory System
KW - pirfenidone
KW - population pharmacokinetics
UR - http://www.scopus.com/inward/record.url?scp=85093961903&partnerID=8YFLogxK
U2 - 10.1016/j.heliyon.2020.e05279
DO - 10.1016/j.heliyon.2020.e05279
M3 - Artículo
AN - SCOPUS:85093961903
SN - 2405-8440
VL - 6
JO - Heliyon
JF - Heliyon
IS - 10
M1 - e05279
ER -