An analysis of the biopharmaceutical behaviour of proton pump inhibitors with different physicochemical properties

Abstract At present, little information on the biopharmaceutical behaviour of proton pump inhibitors (PPIs) describing their absorption and biodistribution in vivo has been reported because the extreme instability of PPIs in the gastrointestinal environment makes it difficult to analyze such behaviour. In this work, a modified rat in situ intestinal perfusion model was employed to investigate absorption in the gastrointestinal tract and subsequent biodistribution of several PPIs (ilaprazole, esomeprazole and rabeprazole), which have different physicochemical properties. Our data indicated that PPIs exhibited significantly enhanced absorption rates in the whole intestine, including the duodenum, jejunum, ileum and colon, corresponding to the increase in the oil-water partition coefficient (LogP). PPIs and corresponding salt types showed no obvious differences in absorption, implying that solubility changes in the PPI have little effect on its absorption in the gastrointestinal tract. Among these PPIs, ilaprazole presented a more stable intestinal absorption behaviour, as well as more distribution and longer residence time in the stomach by HPLC-MS/MS analysis and radioactivity counts after 14C radiolabelling. These results may be useful information for PPI optimization and oral formulation design.