Bases farmacocinéticas de la monitorización de imatinib en pacientes oncológicos

[EN]The widely inter-individual pharmacokinetic variability of the tyrosine-kinase BCR-ABL1 inhibitor imatinib shows a high trough plasma concentration (Cmin) variability at the steady state, after a standard given dosing regimen. Cmin of 16 diagnosed patients of chronic myeloid leukemia from Salama...

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Detalles Bibliográficos
Autores: Arenales Cáceres, Pablo, García Sánchez, María José
Tipo de recurso: artículo
Fecha de publicación:2018
País:España
Institución:Universidad de Salamanca (USAL)
Repositorio:GREDOS. Repositorio Institucional de la Universidad de Salamanca
OAI Identifier:oai:gredos.usal.es:10366/137754
Acceso en línea:http://hdl.handle.net/10366/137754
Access Level:acceso abierto
Palabra clave:imatinib
monitorización de fármacos
modelos farmacocinéticos poblacionales
parámetros farmacocinéticos
PKS
WinPKS
therapeutic drug monitoring
population pharmacokinetic models
pharmacokinetic parameters
Descripción
Sumario:[EN]The widely inter-individual pharmacokinetic variability of the tyrosine-kinase BCR-ABL1 inhibitor imatinib shows a high trough plasma concentration (Cmin) variability at the steady state, after a standard given dosing regimen. Cmin of 16 diagnosed patients of chronic myeloid leukemia from Salamanca Clinical Hospital was measured by HPLC-MS, estimating the main pharmacokinetic parameters by Bayesian methodology. Two clinical pharmacokinetic software: PKS and WinPKS (in development) were used, in which three population pharmacokinetic models were implemented. The main pharmacokinetic parameters estimated are volume of distribution, clearance, half-life time, elimination rate constant and area under the curve. These pharmacokinetic parameters can be used to dosing adjustment by setting the most appropriate maintenance dose and frequency of administration to achieve safe and effective Cmin at the steady state. It has been shown no clinically significant differences among the tested population pharmacokinetic models, but a high pharmacokinetic interindividual variability. These results justify the use of Therapeutic Drug Monitoring as a useful clinical tool in order to optimize the dosing in non-response patients.