The aim of this study is forced oxidative degradation of active pharmaceutical ingredient abacavir, used to treat HIV-infected patients. A fast and sensitive method for the determination of abacavir and its degradation products by ultra-high performance liquid chromatography has been developed and validated, that made it possible to evaluate the oxidation stability of abacavir and Ziagen tablets. Suitable chromatographic separation was achieved using a Kinetex C18 column and gradient elution with a mobile phase consisting of acetonitrile and ammonium acetate (c = 20 mmol dm−3 , pH = 7.0). The total run time was 11 minutes. The determination of abacavir and its degradation products was performed by a photodiode array detector at λ = 254 nm. The optimized method for the determination of abacavir and its degradation products was applied to study the oxidation of abacavir by both traditional and electrochemical approaches. The forced degradation study in solution revealed abacavir instability in the presence of 3% hydrogen peroxide and during electrochemical oxidation. The study found that excipients in the tablet suppress the degradation of abacavir by approximately 10 %. Abacavir is oxidized by 15 % by hydrogen peroxide after 24 hours at 25 řC, after 1.5 hours at 50 řC and after 5 minutes at...

Charles University in Prague Faculty of Pharmacy in Hradec Králové Department of Pharmacology and Toxicology Student: Bc. Michaela Jahodová Supervisor: PharmDr. Lukáš Červený, Ph.D. Title of diploma thesis: In vitro and ex vivo study of drug-drug interactions of antiretrovirals on intestinal ATP-binding drug transporters The absorption of orally administered drugs takes place especially in the intestine, where it can affect by the activity of drug's ABC transporters located on the apical membrane of the intestinal epithelium. Study of drug interactions in intestinal ABC transporters is essential to ensure effective and safe pharmacotherapy. Testing of bi- directional transport on Caco-2 cells is generally the preferred method for in vitro evaluation of substrates and inhibitors of ABC transporters. Drawbacks of the Caco-2 model increase the need and necessity to introduce new models. A great potential is the involvement of ex vivo methodologies in the human or rat intestine. The aim of the work was to introduce an in vitro methodology using the Caco-2 cell monolayer and the ex vivo methodology of precision-cut rat intestinal slices. By the bi-directional transport method, we analyzed drug interactions of the model substrate P-gp and BCRP Rhodamine 123 (RHD123) and clinically-used tenofovir...