Prospective Analysis in GIST Patients on the Role of Alpha-1 Acid Glycoprotein in Imatinib Exposure.

Autor: Bins S; Department of Medical Oncology, Erasmus MC Cancer Institute, PO Box 5201, 3008 AE, Rotterdam, The Netherlands., Eechoute K; Department of Medical Oncology, Erasmus MC Cancer Institute, PO Box 5201, 3008 AE, Rotterdam, The Netherlands., Kloth JS; Department of Medical Oncology, Erasmus MC Cancer Institute, PO Box 5201, 3008 AE, Rotterdam, The Netherlands., de Man FM; Department of Medical Oncology, Erasmus MC Cancer Institute, PO Box 5201, 3008 AE, Rotterdam, The Netherlands., Oosten AW; Department of Medical Oncology, Erasmus MC Cancer Institute, PO Box 5201, 3008 AE, Rotterdam, The Netherlands., de Bruijn P; Department of Medical Oncology, Erasmus MC Cancer Institute, PO Box 5201, 3008 AE, Rotterdam, The Netherlands., Sleijfer S; Department of Medical Oncology, Erasmus MC Cancer Institute, PO Box 5201, 3008 AE, Rotterdam, The Netherlands., Mathijssen RH; Department of Medical Oncology, Erasmus MC Cancer Institute, PO Box 5201, 3008 AE, Rotterdam, The Netherlands. a.mathijssen@erasmusmc.nl.
Jazyk: angličtina
Zdroj: Clinical pharmacokinetics [Clin Pharmacokinet] 2017 Mar; Vol. 56 (3), pp. 305-310.
DOI: 10.1007/s40262-016-0441-0
Abstrakt: Background: For imatinib, a relationship between systemic exposure and clinical outcome has been suggested. Importantly, imatinib concentrations are not stable and decrease over time, for which several mechanisms have been suggested. In this study, we investigated if a decrease in alpha-1 acid glycoprotein (AGP) is the main cause of the lowering in imatinib exposure over time.
Methods: We prospectively measured imatinib trough concentration (C min ) values in 28 patients with gastrointestinal stromal tumours, at 1, 3 and 12 months after the start of imatinib treatment. At the same time points, AGP levels were measured.
Results: Overall, imatinib C min and AGP levels were correlated (r 2  = 0.656; P < 0.001). However, AGP levels did not fluctuate significantly over time, nor did the change in AGP levels correlate with the change in the imatinib C min .
Conclusion: We showed that systemic AGP levels are not likely to be a key player in the decrease in systemic imatinib exposure over time. As long as intra-individual changes in imatinib exposure remain unexplained, researchers should standardize the sampling times for imatinib in order to be able to assess the clinical applicability of therapeutic drug monitoring.
Databáze: MEDLINE
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