The use of therapeutic drug monitoring to highlight an over-looked drug-drug interaction leading to imatinib treatment failure.
Carbamazepine
Drug-drug interaction
Imatinib
Therapeutic drug monitoring
Journal
Daru : journal of Faculty of Pharmacy, Tehran University of Medical Sciences
ISSN: 2008-2231
Titre abrégé: Daru
Pays: Switzerland
ID NLM: 101125969
Informations de publication
Date de publication:
Dec 2023
Dec 2023
Historique:
received:
22
09
2022
accepted:
20
05
2023
medline:
6
11
2023
pubmed:
15
6
2023
entrez:
15
6
2023
Statut:
ppublish
Résumé
Chronic oral anticancer therapies, are increasingly prescribed and present new challenges including the enhanced risk of overlooked drug-drug interactions (DDIs). Lengthy treatments and patients' management by different professionals can lead to serious prescribing errors that therapeutic drug monitoring (TDM) can help identifying thus allowing a more effective and safer treatment of patients with polypharmacy. This report aims to exemplify how an intensified pharmacological approach could help in the clinical monitoring of patients on chronic treatments. A patient with gastrointestinal stromal tumor was referred to our clinical pharmacology service due to tumor progression while on imatinib therapy. The investigation was based on TDM, pharmacogenetics, DDI evaluation and Circulating tumor DNA (ctDNA) analysis. The patient underwent repeated blood samplings to measure imatinib and norimatinib plasma concentrations through a validated LC-MS/MS method. Polymorphisms affecting genes involved in imatinib metabolism and transport were investigated using SNPline PCR Genotyping System. Drug-drug interactions were evaluated though Lexicomp. ctDNA analysis was performed on MiSeq platform. TDM analysis revealed that the patient was underexposed to imatinib (C The active pharmacological monitoring allowed the identification of a dangerous previously over-looked DDI leading to IMA under-exposure. The switch to a different antiepileptic treatment, reversed the effect of DDI, restoring therapeutic IMA plasmatic concentrations.
Sections du résumé
BACKGROUND
BACKGROUND
Chronic oral anticancer therapies, are increasingly prescribed and present new challenges including the enhanced risk of overlooked drug-drug interactions (DDIs). Lengthy treatments and patients' management by different professionals can lead to serious prescribing errors that therapeutic drug monitoring (TDM) can help identifying thus allowing a more effective and safer treatment of patients with polypharmacy.
OBJECTIVES
OBJECTIVE
This report aims to exemplify how an intensified pharmacological approach could help in the clinical monitoring of patients on chronic treatments.
METHODS
METHODS
A patient with gastrointestinal stromal tumor was referred to our clinical pharmacology service due to tumor progression while on imatinib therapy. The investigation was based on TDM, pharmacogenetics, DDI evaluation and Circulating tumor DNA (ctDNA) analysis. The patient underwent repeated blood samplings to measure imatinib and norimatinib plasma concentrations through a validated LC-MS/MS method. Polymorphisms affecting genes involved in imatinib metabolism and transport were investigated using SNPline PCR Genotyping System. Drug-drug interactions were evaluated though Lexicomp. ctDNA analysis was performed on MiSeq platform.
RESULTS
RESULTS
TDM analysis revealed that the patient was underexposed to imatinib (C
CONCLUSION
CONCLUSIONS
The active pharmacological monitoring allowed the identification of a dangerous previously over-looked DDI leading to IMA under-exposure. The switch to a different antiepileptic treatment, reversed the effect of DDI, restoring therapeutic IMA plasmatic concentrations.
Identifiants
pubmed: 37318715
doi: 10.1007/s40199-023-00465-z
pii: 10.1007/s40199-023-00465-z
pmc: PMC10624793
doi:
Substances chimiques
Imatinib Mesylate
8A1O1M485B
Antineoplastic Agents
0
Carbamazepine
33CM23913M
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
267-272Informations de copyright
© 2023. The Author(s).
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