Cargando…

Pharmacokinetics of Four Tyrosine Kinase Inhibitors in Adult and Paediatric Chronic Myeloid Leukaemia Patients

Tyrosine kinase inhibitors work by blocking the tyrosine kinases responsible for the dysregulation of intracellular signalling pathways in tumour cells. This study looked at the impact of age and sex on the levels of imatinib, dasatinib, nilotinib, and ponatinib in plasma and cerebrospinal fluid sam...

Descripción completa

Detalles Bibliográficos
Autores principales: Allegra, Sarah, Dondi, Emma, Chiara, Francesco, De Francia, Silvia
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10525795/
https://www.ncbi.nlm.nih.gov/pubmed/37760918
http://dx.doi.org/10.3390/biomedicines11092478
_version_ 1785110869821095936
author Allegra, Sarah
Dondi, Emma
Chiara, Francesco
De Francia, Silvia
author_facet Allegra, Sarah
Dondi, Emma
Chiara, Francesco
De Francia, Silvia
author_sort Allegra, Sarah
collection PubMed
description Tyrosine kinase inhibitors work by blocking the tyrosine kinases responsible for the dysregulation of intracellular signalling pathways in tumour cells. This study looked at the impact of age and sex on the levels of imatinib, dasatinib, nilotinib, and ponatinib in plasma and cerebrospinal fluid samples of patients with chronic myeloid leukaemia. Imatinib and dasatinib were used to treat the majority of the enrolled patients, and most of them were paediatrics. A total of 82.4% of the patients were men; however, sex-related differences in the drugs’ pharmacokinetics were not found. Age and imatinib plasma concentration were found to be inversely correlated. The dasatinib concentrations in plasma were found to be substantially lower than those found in cerebrospinal fluid, particularly in paediatrics. Analysing the obtained data, we can state that therapeutic drug monitoring is a useful method for adjusting a patient’s treatment schedule that depends on drug concentrations in biological fluids. The use of therapeutic drug monitoring in conjunction with tyrosine kinase inhibitors for the treatment of chronic myeloid leukaemia is supported by a number of sources of evidence. As a result, as the research develops, the tyrosine kinase inhibitor therapeutic drug monitoring classification needs to be refined in terms of factors like sex and age.
format Online
Article
Text
id pubmed-10525795
institution National Center for Biotechnology Information
language English
publishDate 2023
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-105257952023-09-28 Pharmacokinetics of Four Tyrosine Kinase Inhibitors in Adult and Paediatric Chronic Myeloid Leukaemia Patients Allegra, Sarah Dondi, Emma Chiara, Francesco De Francia, Silvia Biomedicines Article Tyrosine kinase inhibitors work by blocking the tyrosine kinases responsible for the dysregulation of intracellular signalling pathways in tumour cells. This study looked at the impact of age and sex on the levels of imatinib, dasatinib, nilotinib, and ponatinib in plasma and cerebrospinal fluid samples of patients with chronic myeloid leukaemia. Imatinib and dasatinib were used to treat the majority of the enrolled patients, and most of them were paediatrics. A total of 82.4% of the patients were men; however, sex-related differences in the drugs’ pharmacokinetics were not found. Age and imatinib plasma concentration were found to be inversely correlated. The dasatinib concentrations in plasma were found to be substantially lower than those found in cerebrospinal fluid, particularly in paediatrics. Analysing the obtained data, we can state that therapeutic drug monitoring is a useful method for adjusting a patient’s treatment schedule that depends on drug concentrations in biological fluids. The use of therapeutic drug monitoring in conjunction with tyrosine kinase inhibitors for the treatment of chronic myeloid leukaemia is supported by a number of sources of evidence. As a result, as the research develops, the tyrosine kinase inhibitor therapeutic drug monitoring classification needs to be refined in terms of factors like sex and age. MDPI 2023-09-07 /pmc/articles/PMC10525795/ /pubmed/37760918 http://dx.doi.org/10.3390/biomedicines11092478 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Allegra, Sarah
Dondi, Emma
Chiara, Francesco
De Francia, Silvia
Pharmacokinetics of Four Tyrosine Kinase Inhibitors in Adult and Paediatric Chronic Myeloid Leukaemia Patients
title Pharmacokinetics of Four Tyrosine Kinase Inhibitors in Adult and Paediatric Chronic Myeloid Leukaemia Patients
title_full Pharmacokinetics of Four Tyrosine Kinase Inhibitors in Adult and Paediatric Chronic Myeloid Leukaemia Patients
title_fullStr Pharmacokinetics of Four Tyrosine Kinase Inhibitors in Adult and Paediatric Chronic Myeloid Leukaemia Patients
title_full_unstemmed Pharmacokinetics of Four Tyrosine Kinase Inhibitors in Adult and Paediatric Chronic Myeloid Leukaemia Patients
title_short Pharmacokinetics of Four Tyrosine Kinase Inhibitors in Adult and Paediatric Chronic Myeloid Leukaemia Patients
title_sort pharmacokinetics of four tyrosine kinase inhibitors in adult and paediatric chronic myeloid leukaemia patients
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10525795/
https://www.ncbi.nlm.nih.gov/pubmed/37760918
http://dx.doi.org/10.3390/biomedicines11092478
work_keys_str_mv AT allegrasarah pharmacokineticsoffourtyrosinekinaseinhibitorsinadultandpaediatricchronicmyeloidleukaemiapatients
AT dondiemma pharmacokineticsoffourtyrosinekinaseinhibitorsinadultandpaediatricchronicmyeloidleukaemiapatients
AT chiarafrancesco pharmacokineticsoffourtyrosinekinaseinhibitorsinadultandpaediatricchronicmyeloidleukaemiapatients
AT defranciasilvia pharmacokineticsoffourtyrosinekinaseinhibitorsinadultandpaediatricchronicmyeloidleukaemiapatients