Mucosal irritative and healing impairment action of risedronate in rat stomachs: Comparison with alendronate

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<jats:title>Abstract</jats:title><jats:p><jats:bold>Background and Aim: </jats:bold> We used alendronate and risedronate as bisphosphonates and examined whether or not these agents have a mucosal irritative action in the stomach and impair the healing of pre‐existing gastric ulcers in rats.</jats:p><jats:p><jats:bold>Methods: </jats:bold> Male Sprague Dawley (SD) rats were used in the following two studies: (i) the effects of risedronate and alendronate on gastric potential difference (PD), gastric mucosal blood flow (GMBF) and acid back‐diffusion in the stomach mounted on <jats:italic>ex vivo</jats:italic> chamber under urethane anesthesia and; (ii) the influence of daily treatment with these drugs on the healing of acetic acid‐induced gastric ulcers was examined.</jats:p><jats:p><jats:bold>Results: </jats:bold> Mucosal application of risedronate produced PD reduction in the saline‐perfused stomachs in a dose‐dependent manner. Alendronate also produced a marked PD reduction, the effect being more potent than that of risedronate. In the stomach exposed to acid (100 mM HCl), both drugs produced a marked reduction in PD, followed by acid back‐diffusion and a small increase in GMBF, resulting in hemorrhagic lesions, and the effects again were more pronounced with alendronate. These irritative effects were dependent on the pH of drug solution and the action was more potent at pH 7 than pH 4. Conversely, the healing of acetic acid‐induced gastric ulcers was significantly delayed by daily administration of these drugs, yet this effect was less pronounced in the case of risedronate. The healing impairing effect of these bisphosphonates was potentiated by coadministration of indomethacin.</jats:p><jats:p><jats:bold>Conclusion: </jats:bold> Both alendronate and risedronate have mucosal irritative and healing impairing effects in the stomach, yet the effect of risedronate was much less pronounced compared to alendronate. It is assumed that risedronate is safer than alendronate as the antiresorptive agent in patients with diseases related to bone remodeling.</jats:p>

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