scholarly journals Individualization of Drug Therapy Mode in a Patient with Disseminated Form of GIST by Determining Active Metabolites of the Drug (Tyrosine Kinase Inhibitor) in Blood Plasma

2019 ◽  
Vol 2 (17) ◽  
pp. 38-42
Author(s):  
S. T. Adleyba ◽  
L. M. Kogonia ◽  
L. E. Gurevich ◽  
A. V. Sidorov
Keyword(s):  
High Performance Liquid Chromatography ◽  
Liquid Chromatography ◽  
Tyrosine Kinase ◽  
Blood Plasma ◽  
Tyrosine Kinase Inhibitors ◽  
High Performance ◽  
Kinase Inhibitors ◽  
Kinase Inhibitor ◽  
Response To Therapy ◽  
Active Metabolites

An own experience of effective treatment of a patient with a disseminated form of gastrointestinal stromal tumor (GIST) with a preparation from the group of tyrosine kinase inhibitors (imatinib) is presented.Relevance. Therapy of gastrointestinal stromal tumors is still a complex problem of modern oncology. Since 2001, a breakthrough has occurred in the treatment of patients with GISTO due to the successful use of a targeted drug from the group of tyrosine kinase inhibitors — imatinib, which is effective in the first line of inoperable and / or metastatic GISTs, and is also used for the neoadjuvant, adjuvant therapy of localized GISTs. The lack of response to therapy and, consequently, the progression of the disease, may be associated with a decrease in the therapeutic concentration of imatinib in the blood plasma. Determining the concentration of active metabolites of imatinib in the serum allows timely identification of potential causes of insufficient response to therapy and individual correction of the dose of the drug.Materials and methods. In order to determine the significance of the correlation between increasing / decreasing the dose of imatinib and achieving a therapeutic response, we used a laboratory method of high performance liquid chromatography to determine the concentration of imatinib in serum.Conclusion. Determination of the reduced concentration of active metabolites of imatinib in the blood plasma by high performance liquid chromatography with the detection of tandem mass spectrometry in a patient with disseminated form of GIST allowed to correct the dose of the drug and achieve a positive effect.

scholarly journals Ultra High Performance Liquid Chromatography Method for the Determination of Two Recently FDA Approved TKIs in Human Plasma Using Diode Array Detection

2015 ◽  
Vol 2015 ◽  
pp. 1-6 ◽  
Author(s):  
Marwa Fouad ◽  
Maxime Helvenstein ◽  
Bertrand Blankert
Keyword(s):  
High Performance Liquid Chromatography ◽  
Liquid Chromatography ◽  
Tyrosine Kinase ◽  
Human Plasma ◽  
Tyrosine Kinase Inhibitors ◽  
High Performance ◽  
Kinase Inhibitors ◽  
Therapeutic Window ◽  
Therapeutic Drug

Generally, tyrosine kinase inhibitors have narrow therapeutic window and large interpatient variability compared to intrapatient variability. In order to support its therapeutic drug monitoring, two fast and accurate methods were developed for the determination of recently FDA approved anticancer tyrosine kinase inhibitors, afatinib and ibrutinib, in human plasma using ultra high performance liquid chromatography coupled to PDA detection. Diclofenac sodium was used as internal standard. The chromatographic separation was achieved on an Acquity UPLC BEH C18 analytical column using a mobile phase combining ammonium formate buffer and acetonitrile at a constant flow rate of 0.4 mL/min using gradient elution mode. AµSPE (solid phase extraction) procedure, using Oasis MCXµElution plates, was processed and it gave satisfying and reproducible results in terms of extraction yields. Additionally, the methods were successfully validated using the accuracy profiles approach (β= 95% and acceptance limits = ±15%) over the ranges 5–250 ng/mL for afatinib and from 5 to 400 ng/mL for ibrutinib in human plasma.

scholarly journals CLINICAL EXPERIENCE IN USING TARGETED THERAPY FOR DISSEMINATED GASTROINTESTINAL STROMAL TUMORS

2019 ◽  
Vol 18 (3) ◽  
pp. 109-113
Author(s):  
S. T. Adlejba ◽  
L. M. Kogonija ◽  
L. E. Gurevich ◽  
A. V. Sidorov
Keyword(s):  
Mass Spectrometry ◽  
High Performance Liquid Chromatography ◽  
Liquid Chromatography ◽  
Gastrointestinal Stromal Tumors ◽  
High Performance ◽  
Response To Therapy ◽  
Tandem Mass ◽  
Active Metabolites ◽  
Stromal Tumors

We report a case of disseminated gastrointestinal stromal tumor effectively treated with imatinib, a selective tyrosine kinase inhibitor.Background.Treatment of gastrointestinal stromal tumors (GIST ) still remains a clinical challenge. Since 2001 a breakthrough has occurred in the treatment of patients with GIST due to a successful use of imatinib, the targeted drug from the group of tyrosine kinase inhibitors, which is effective in the first line of inoperable and/or metastatic GIST , and is also used for neoadjuvant and adjuvant therapy for localized GIST . Genetic mutational analysis used for the correct prescription of targeted therapy suggests that it is inappropriate to administer imatinib in patients with a mutation in the succinate dehydrogenase gene and D842V mutation in the platelet-derived growth factor gene. However, in different regions of the Russian Federation, such diagnostic procedure may not always be available for a number of technical reasons. The lack of response to therapy and, consequently, the progression of the disease, may be associated with a decrease in the therapeutic concentration of imatinib in the blood plasma. Determination of the concentration of active metabolites of imatinib in the serum allows timely identification of potential causes of insufficient response to therapy and individual correction of the dose of the drug.Material and Methods.To assess a significance of the correlation between increasing/decreasing the dose of imatinib and achieving a therapeutic response, we used a laboratory high-performance liquid chromatography method to determine the concentration of imatinib in serum.Conclusion.Determination of a decreased concentration of active metabolites of imatinib in plasma by high-performance liquid chromatography with detection of tandem mass spectrometry method in a patient with disseminated GIST allowed us to correct the dose of the drug and achieve a positive effect with a duration of 51 months (since the dose was increased). The method of high-performance liquid chromatography with the detection of the method of tandem mass spectrometry is not an absolute alternative to gene mutation analysis, however, it can be effectively used for correction of the dose of imatinib in patients with GIST.

scholarly journals Thrombotic microangiopathy in dasatinib-treated patients with chronic myeloid leukemia

2019 ◽  
Vol 4 (1-2) ◽  
pp. 41-45 ◽  
Author(s):  
Takeo Koshida ◽  
Sylvia Wu ◽  
Hitoshi Suzuki ◽  
Rimda Wanchoo ◽  
Vanesa Bijol ◽  
...  
Keyword(s):  
Chronic Myeloid Leukemia ◽  
Tyrosine Kinase ◽  
Tyrosine Kinase Inhibitor ◽  
Tyrosine Kinase Inhibitors ◽  
Thrombotic Microangiopathy ◽  
Myeloid Leukemia ◽  
Kinase Inhibitors ◽  
Kidney Biopsy ◽  
Kinase Inhibitor ◽  
Target Effect

Dasatinib is the second-generation tyrosine kinase inhibitor used in the treatment of chronic myeloid leukemia. Proteinuria has been reported with this agent. We describe two kidney biopsy–proven cases of dasatinib-induced thrombotic microangiopathy that responded to stoppage of dasatinib and using an alternate tyrosine kinase inhibitor. Certain specific tyrosine kinase inhibitors lead to endothelial injury and renal-limited thrombotic microangiopathy. Hematologists and nephrologists need to be familiar with this off-target effect of dasatinib.

Sign in / Sign up

Export Citation Format

Share Document