Mucosal irritative and healing impairment action of risedronate in rat stomachs: Comparison with alendronate
Mucosal irritative and healing impairment action of risedronate in rat stomachs: Comparison with alendronate
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DOI：
10.1111/j.1440-1746.2003.03314.x
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发表时间：
2004-05-01
影响因子：
4.1
通讯作者：
Takeuchi, K
中科院分区：
文献类型：
--
作者：
Kanatsu, K;Aihara, E;Takeuchi, K
背景与目的：以阿仑膦酸盐和利塞膦酸盐为双膦酸类药物，观察其对胃粘膜的刺激性作用及对大鼠胃溃疡愈合的影响。方法：采用SD雄性大鼠，在乌拉坦麻醉下，观察利塞膦酸盐和阿仑膦酸盐对胃电势差(PD)、胃粘膜血流量(GMBF)和胃酸反扩散的影响；结果：在生理盐水灌流的大鼠胃粘膜内应用利塞膦酸后，PD减少，且呈剂量依赖关系。阿伦磷酸钠也能显著降低帕金森病患者的帕金森病发生率，其作用强于利塞磷酸钠。在暴露于酸(100 MMHCl)的胃中，两种药物均使PD显著减少，随后酸反向扩散，GMBF略有增加，导致出血性病变，而阿仑磷酸钠的作用再次更为明显。这些刺激性作用依赖于药物溶液的pH，并且在pH为7时的刺激作用比在pH为4时更强。相反，这些药物的每日给药显著延缓了醋酸性胃溃疡的愈合，而利塞磷酸钠的这种作用不那么明显。结论：阿仑膦酸盐和利塞膦酸盐对胃粘膜均有刺激和愈合损伤作用，但利塞膦酸盐的作用不如阿仑膦酸盐明显。在与骨重建相关的疾病中，利塞膦酸盐作为抗吸收药物比阿仑磷酸钠更安全。(C)2004年Blackwell出版亚洲私人有限公司。
Background and Aim: 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 preexisting gastric ulcers in rats.Methods: 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 ex vivo 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.Results: 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.Conclusion: 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. (C) 2004 Blackwell Publishing Asia Pty Ltd.