National Repository of Grey Literature 2 records found  Search took 0.00 seconds. 
Physiological and pathological factors affecting absorption of drugs
Ryšánek, Pavel ; Šíma, Martin (advisor) ; Mičuda, Stanislav (referee) ; Dražanová, Eva (referee)
Absorption of drugs from the gastrointestinal tract after oral administration is a key pharmacokinetic process co-determining the subsequent pharmacodynamic response of the organism and therapeutic efficacy. This dissertation thesis is devoted to the study of factors that influence this parameter. Special emphasis is placed on the study of lymphatic absorption, i.e. the rate of absorption of the active substance via the intestinal lymphatic system. A number of in vivo studies have been carried out in laboratory rats. Pharmacokinetic studies have been performed by means of regular blood sampling from vascular catheters after oral administration of the drug. Lymphatic absorption was investigated in an anaesthetized mesenteric lymphatic duct cannulated rat model. Modern drugs were tested that were incorporated into innovative dosage forms by collaborating chemical and technological institutions. Abiraterone acetate, a lipophilic agent used in the therapy of prostate cancer, was well absorbed from the gastrointestinal tract after administration in the form of oil marbles. This technology also succeeded in reducing the otherwise very significant positive food-effect. Abiraterone acetate was not absorbed to any significant extent via the intestinal lymphatic system. In contrast, lymphatic absorption of...
DEVELOPMENT OF A UHPLC-MS/MS METHOD FOR NILOTINIB DETERMINATION IN RAT SERUM
Černá, Kateřina ; Kozlík, Petr (advisor) ; Křížek, Tomáš (referee)
This bachelor thesis aimed to develop a UHPLC-MS/MS method for the determination of nilotinib in rat serum. The developed UHPLC-MS/MS method was used to monitor the pharmacokinetic release of the active substance in a rat model organism in a project focused on the formulation of a tablet containing nilotinib with a slower release than before. The optimal conditions of the method were as follows. Chromatographic column Acquity UPLC BEH PHENYL 100x2.1 mm, 1.7 μm from Waters. The mobile phase consisted of methanol and distilled water, both with the addition of 0.1% formic acid using gradient elution. The flow rate of the mobile phase was 0.3 mL/min, the temperature in an autosampler 15 řC, the column temperature 40 řC, the analysis time 6.5 minutes, and the injection volume 2 μl. The MRM transition monitored for nilotinib was: 530.2 → 289.10 (Q1 = -26 V; CE = -31 V; Q3 = -20 V) and for nilotinib D6: 536.2 → 295.15 (Q1 = -26 V; CE = -31 V; Q3 = -14 V). The setting of the ion source was as follows: nebulizing gas flow 3 L/min; drying gas flow 10 L/min; source temperature 300 řC; desolvation capillary temperature 250 řC. The method was partially validated. The coefficient of determination 1.0000 shows the excellent linearity of the method. The accuracy, expressed as a relative error, was up to 20 %. The...

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