To measure organic cation transporter 1 (OCT1) uptake activity, which corresponds to the intracellular uptake and retention (IUR) of imatinib, mononuclear cells and granulocytes were incubated with imatinib in the presence or absence of prazosin. After sample preparation and additional concentration the intracellular concentration of imatinib was determined by LC-MS/MS method. With different experimental setups we have demonstrated the ability to i) measure the intracellular imatinib concentrations, ii) to measure the IUR without any radiolabeled markers and even iii) to measure the IUR in cells obtained from patients already on imatinib therapy without any pause in the therapy itself.
B.03 Paper at an international scientific conference
COBISS.SI-ID: 3308145This contribution describes the importance of therapeutic drug monitoring of tyrosine kinase inhibitors (TKI) in the plasma and blood of patients with chronic myeloic leukemia (CML). Several studies have confirmed for imatinib the link between its plasma concentration and the achievement of the major molecular response. Monitoring of TKI blood concentrations also enables the dose adjustments in each individual patient. Furthermore, it also enables monitoring of adherence to therapy, which is recognized as one of the key factors determining the long-term success of treatment with TKI. The method presented allows the simultaneous measurement of the three most commonly used TKIs: imatinib, nilotinib and dasatinib in dried blood spots (DBS), which provides some important advantages over the classic withdrawal of venous blood, for example. much smaller sample volume: 10 µL, blood sampling by the patients at home, sending samples by mail, and easier storage. The method was validated according to the U.S. Food and Drug Administration (FDA) guidelines and successfully applied to the samples from Slovenian patients with CML.
B.03 Paper at an international scientific conference
COBISS.SI-ID: 3234161At the fourth haematological congress of Slovenia we presented the basic outlay of this research project; the concept of imatinib active transport by OCT1 and its intracellular uptake and retention (IUR). The relevance of these parameters for the therapy of CML was presented on the basis of existing literature. We explained the methods being developed for the direct measurement of IUR in the blood cells without the use of radioactively labeled drug. The results obtained with the isolated leukocytes of a volunteer and with the K562 cell line were presented as a proof of concept.
B.03 Paper at an international scientific conference
COBISS.SI-ID: 3233905