Applied Cancer Research Institution for Translational Oncology

Austria

Applied Cancer Research Institution for Translational Oncology

Austria
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Buchner P.,University of Vienna | Sahmanovic A.,University of Vienna | Schreiber V.,University of Vienna | Baroian N.,University of Vienna | And 3 more authors.
Pharmacology | Year: 2015

Before being able to develop a pharmacodynamic effect, a number of drugs have to be activated by enzymes, which are known to be potentially influenced by manifold factors, leading to a possible alteration of their activity behaviour. Based on capecitabine, we report a simple and rapid method for the estimation and comparison of the so-called 'apparent enzyme activity' (R), not only intra- (different dose levels) but also inter-schedule, to contribute to therapeutic success. Dividing the area under the curve (AUC) of the product by the AUC of the precursor generates a factor which indicates the apparent activity of the enzyme involved in the biotransformation of a compound. Our own data as well as data from the literature was used to calculate those R levels revealing that the formation of 5′-DFUR - the immediate precursor of 5-fluorouracil - was not affected by concomitant medication within the dosing range investigated. Calculated hypothetical means of R for carboxylesterase (1.49 ± 0.66) and for cytidine deaminase (1.17 ± 0.65) were obtained. Additionally, it is important to note that the method described in this report is of general use and not limited to chemotherapeutic agents, as soon as enzymes are involved in drug activation. © 2015 S. Karger AG, Basel.


Buchner P.,University of Vienna | Mihola E.,University of Vienna | Sahmanovic A.,University of Vienna | Steininger T.,Applied Cancer Research Institution for Translational Oncology | And 4 more authors.
Anticancer Research | Year: 2013

A simple and precise analytical method for the determination of 5'deoxy-5-fluorocytidine (DFCR) and 5'deoxy-5-fluorouridine (DFUR), the enzymatically formed metabolites of capecitabine in plasma, was developed using a reversed-phase high performance liquid chromatography gradient method with external standard method. Blood samples were analyzed after separation of DFCR/DFUR by solid-phase extraction from matrix compounds using a C16 amide reversed-phase column operated at a flow rate of 0.8 ml/min in gradient elution mode with a mobile phase composed of water-methanol (10 mM ammonium acetate in water; m/v). Excellent recoveries in plasma ranging from 77.5- 99.12% for DFCR and 84.70-99.15% for DFUR, respectively, were obtained. For both compounds the calibration curves were linear over the range from 0.156 to 5.0 μg/ml. The present assay is robust, selective and sensitive, and is being applied in our laboratories to monitor plasma concentrations of DFCR and DFUR in clinical phase I and phase II studies.

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