Bioequivalence studies are usually conducted with healthy volunteers. However, there are some differences in conditions of enteric-coated acid-labile drug release and absorption between healthy subjects and gastrointestinal patients. Pathologic duodenogastric reflux (PDGR) with high-amplitude changes in gastric pH can lead to destruction of the coating layer, resulting in degradation of the active compounds due to decrease in pH level after a reflux. The pH increasing ≥4 within PPIs administration also promotes dissolution of poor-quality coating. Modified comparative dissolution testing of original omeprazole (OO) and Generics1;2;3;4 proceeded in two stages. At first, we moved drugs from solution with Ph=1.2 (1.2 ± 0.05) to рН=7.0 (7.0 ± 0.05) and examined concentration of omeprazole in solution using high-performance liquid chromatography (HPLC). According to our self-developed formula, pH 7 exposure time of resistance to PDGR for omeprazole is 4 minutes, i.e. the active substance should not be released within 4 minutes at pH 7. The exposure at the second stage was conducted with pH 4 (4.0 ± 0.05), which imitated gastric pH after PPI administration. And then we also moved drugs to pH 7 with the subsequent measurement of omeprazole concentration. Omeprazole concentrations after 4, 10, 15, 20, 30, 45, 60 minutes in pH 7 solution at the first stage (pH 1.2 exposure) were different for OO and generics. For OO, these values were 4,7 ± 0,7%; 41,4 ± 3,0%; 62,8 ± 4,0%; 79,5 ± 2,9%; 83,5 ± 2,9%; 81,6 ± 2,9% (partly degradation of omeprazole); 80,6 ± 4,4%; for Generic1 - 0; 49,3 ± 9,9%; 88,8 ± 2,8%; 90,4 ± 3,7%; 88, 2 ± 2,2%; 87,3 ± 2,0%; 85,9 ± 1,1%; for Generic2 - 0; 30, 6 ± 6,3%; 66,7 ± 8,2%; 76,4 ± 7,4%; 82,8 ± 5,3%; 86,0 ± 3,7%; 84,6 ± 3,3%: for Generic3 - 80,8 ± 3,6%; 83,5 ± 1,9%; 83, 8 ± 3,2%; 83,3 ± 2,7%; 81,9 ± 2,1%; 82,1 ± 2,0%; 82,0 ± 2,4%; for Generic4 - 82,5 ± 1,7%; 84,4 ± 0,8%; 84,2 ± 1,2%; 82, 9 ± 0,9%; 82,9 ± 0,9%; 82,9 ± 0,9%; 82,8 ± 1,1%, respectively. An analysis of the omeprazole concentration in pH 7 solution at the second stage (pH 4 exposure) revealed the following parameters after 4, 10, 15, 20, 30, 45, 60 minutes: for OO - 4,4 ± 0,6%; 40, 5 ± 3,0%; 62,8 ± 2,0%; 80,0 ± 3,1%; 85,4 ± 2,9%; 82,8 ± 3,4%; 80,9 ± 3,5%; for Generic1 – 0; 67,0 ± 7,8%; 89,7 ± 2,3%; 91, 9 ± 4,3%; 89,1 ± 1,6%; 88,3 ± 1,4%; 87,8 ± 1,2%; for Generic2 – 0; 42,2 ± 5,6%; 75,1 ± 7,3%; 81,0 ± 6,0%; 88,4 ± 3,2%; 88, 6 ± 1,3%; 87,9 ± 1,0%; for Generic4 – 85,5 ± 0,5%; 85,6 ± 0,5%; 84,7 ± 0,9%; 82,7 ± 3,0%; 84,4 ± 0,3%; 84,4 ± 0,3%; 84,3 ± 0,4%, respectively. Generic3 release and degradation were completely realized at pH 4. Gastric stability of Generic3 and Generic4 has been decreasing due to PDGR and pharmacodynamic effect of the PPIs themselves.