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Patients in intensive care often develop stress-induced ulcers. As a preventive measure, proton pump inhibitors (PPIs) are administered by nasogastric tube. However, some PPIs can block the tube. The aim of this study was to compare the behaviour of three PPIs (omeprazole, lanzoprazole and esomeprazole) during the transit of the granules through the tube and to optimise their modes of administration. For each IPP, the experiment was designed to study the influence of four variables: the tube material (silicone or polyurethane), the solvent used to dilute the granules (water or apple juice), the mode of administration (in two or three doses) and the rinse volume (10 or 20 ml). We counted the granules before transit and at the tube outlet, and assayed the active drug ingredient by UV spectrometry. The assay showed complete transit of esomeprazole through the tube, but average losses of omeprazole and lanzoprazole of 39 and 33%, respectively, were observed. No significant improvement was obtained by the variables ‘diluent’ and ‘mode of administration’. The variable ‘rinse’ had a significant influence. For lanzoprazole, a polyurethane tube allowed recovery of on average 86% of the active ingredient. Esomeprazole is thus the choice PPI for the treatment of patients by nasogastric tube. Using a polyurethane tube and a rinse volume of 20 ml, the administration of lanzoprazole by tube can be considered. Use of omeprazole is not recommended because none of the modes of administration tested ensured that a sufficient concentration of active ingredient reached the stomach.