Therapeutic Drug Monitoring of Ivacaftor, Lumacaftor, Tezacaftor, and Elexacaftor in Cystic Fibrosis: Where Are We Now?
Details
Serval ID
serval:BIB_0CAC2AC96B31
Type
Article: article from journal or magazin.
Publication sub-type
Review (review): journal as complete as possible of one specific subject, written based on exhaustive analyses from published work.
Collection
Publications
Institution
Title
Therapeutic Drug Monitoring of Ivacaftor, Lumacaftor, Tezacaftor, and Elexacaftor in Cystic Fibrosis: Where Are We Now?
Journal
Pharmaceutics
ISSN
1999-4923 (Print)
ISSN-L
1999-4923
Publication state
Published
Issued date
11/08/2022
Peer-reviewed
Oui
Volume
14
Number
8
Pages
1674
Language
english
Notes
Publication types: Journal Article ; Review
Publication Status: epublish
Publication Status: epublish
Abstract
Drugs modulating the cystic fibrosis transmembrane conductance regulator (CFTR) protein, namely ivacaftor, lumacaftor, tezacaftor, and elexacaftor, are currently revolutionizing the management of patients with cystic fibrosis (CF), particularly those with at least one F508del variant (up to 85% of patients). These "caftor" drugs are mainly metabolized by cytochromes P450 3A, whose enzymatic activity is influenced by environmental factors, and are sensitive to inhibition and induction. Hence, CFTR modulators are characterized by an important interindividual pharmacokinetic variability and are also prone to drug-drug interactions. However, these CFTR modulators are given at standardized dosages, while they meet all criteria for a formal therapeutic drug monitoring (TDM) program that should be considered in cases of clinical toxicity, less-than-expected clinical response, drug or food interactions, distinct patient subgroups (i.e., pediatrics), and for monitoring short-term adherence. While the information on CFTR drug exposure-clinical response relationships is still limited, we review the current evidence of the potential interest in the TDM of caftor drugs in real-life settings.
Keywords
CFTR modulators, LC–MS/MS, PK/PD, TDM, caftor, cystic fibrosis, dose–effect relationship, elexacaftor, ivacaftor, lumacaftor, plasma level, tezacaftor, therapeutic drug monitoring
Pubmed
Web of science
Open Access
Yes
Create date
06/09/2022 11:39
Last modification date
02/05/2024 7:09