Bases farmacocinéticas de la monitorización de imatinib en pacientes oncológicos

  1. ARENALES CÁCERES, Pablo
  2. GARCÍA SÁNCHEZ, María José 1
  1. 1 Departamento de Ciencias Farmacéuticas. Área de Farmacia y Tecnología Farmacéutica. Universidad de Salamanca. Campus Miguel de Unamuno. Salamanca
Journal:
Farmajournal

ISSN: 2445-1355

Year of publication: 2018

Volume: 3

Issue: 1

Pages: 25-33

Type: Article

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Abstract

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.

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