Journal
PHARMACEUTICS
Volume 14, Issue 8, Pages -Publisher
MDPI
DOI: 10.3390/pharmaceutics14081674
Keywords
TDM; therapeutic drug monitoring; plasma level; PK; PD; dose-effect relationship; cystic fibrosis; LC-MS; MS; CFTR modulators; caftor; ivacaftor; lumacaftor; tezacaftor; elexacaftor
Categories
Funding
- Cystic Fibrosis Switzerland [2022]
- University of Lausanne
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Drugs modulating the CFTR protein have revolutionized the management of cystic fibrosis patients. However, there is significant interindividual pharmacokinetic variability and potential drug-drug interactions. Monitoring drug levels may be important in cases of toxicity, inadequate response, and drug or food interactions.
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.
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