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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...
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Development of an UHPLC method for determination of abiraterone acetate and its oxidative degradation
Vlčková, Nikol ; Křížek, Tomáš (advisor) ; Kubíčková, Anna (referee)
Aim of this thesis was to develop and validate a method for determination of pharmaceutical active substance abiraterone acetate for UHPLC and also to perform forced degradation with 0,3 % hydrogen peroxide and elevated temperatures. Because of poor solubility of abiraterone acetate in water, mixture of acetonitrile of water in ratio of 1:1 was chosen as solvent. Opimized separation was performer on the column Acquity CSH PHENYL-HEXYL (1.7 µm, 100 × 2.1 mm) and its temperature was 45 řC. Mobile phaze was composed of acetonitrile and 0.1 % aqueous solution of formic acid, flow of mobile phase was 0,3 ml/min, sample injection volume was 1 µl and gradient elution was used. UV/VIS detector with diode array was used at the 265 nm wavelenght. Quadrupole mass detector was used as well. For validation of the method repeatability, recovery and limits of detection and quantitation were tested. Calibration dependence was tested in the concentration in range of 0.1-1∙10-4 mg/ml. Forced degradation was carried out on two sets of samples. Hydrogen peroxide of 0.3 % mass concentration was added to one set. Both of the sets were exposed to laboratory temperature and to temperature o 50 řC for 1, 2, 3 days. Abiraterone acetate exhibited small extent of degradation without hydrogen peroxide in laboratory conditions...
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