Orphan drugs, designed to treat rare diseases affecting a small population, pose unique challenges in terms of therapeutic drug monitoring (TDM) due to limited patient data and variability in drug response. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) has emerged as a powerful tool for precise and sensitive drug quantification and can support therapeutic interventions for orphan drug-treated patients. The application of LC-MS/MS in TDM of orphan drugs is presented with a focus on cystic fibrosis transmembrane conductance regulator (CFTR) modulators.
Cystic fibrosis (CF) is a genetic disease that affects an estimated 160,000 people worldwide. CFTR-modulators, such as ivacaftor, tezacaftor, and elexacaftor, have revolutionized the treatment landscape for CF patients by addressing the underlying genetic defects. The efficacy of these drugs is highly variable among individuals due to factors like genotype heterogeneity and pharmacokinetic variations. However, drug-drug-interactions and interpatient variability in drug metabolism necessitate careful monitoring to prevent toxicity or suboptimal treatment. The use of LC-MS/MS in the TDM of CFTR-modulators can help to optimize therapeutic outcomes, minimize adverse side effects and can improve the understanding of the interplay between drug concentrations and clinical response.
In summary, LC-MS/MS plays a pivotal role in TDM and can support the safe and effective use of drugs in rare diseases. Focusing on CFTR-modulators illustrates the versatility of LC-MS/MS in tailoring treatment strategies for individuals facing unique and often challenging medical conditions. As precision medicine continues to advance, the integration of LC-MS/MS into routine clinical practice holds immense promise for optimizing therapeutic outcomes and improving the overall management of orphan drug-treated patients. [1]
Literature:
[1] K. Habler, A.-S. Kalla, M. Rychlik, M. Bruegel, D. Teupser, S. Nährig, M. Vogeser, M. Paal, Isotope dilution LC-MS/MS quantification of the cystic fibrosis transmembrane conductance regulator (CFTR) modulators ivacaftor, lumacaftor, tezacaftor, elexacaftor, and their major metabolites in human serum, Clinical chemistry and laboratory medicine 60 (2022) 82–91.
