Peter C P, Handt L K, Smith S M
Merck Research Laboratories, West Point, Pennsylvania 19486, USA.
Dig Dis Sci. 1998 Sep;43(9):1998-2002. doi: 10.1023/a:1018894827961.
Animal studies were done using an in vivo dog model to examine the possible mechanism for the esophageal adverse events reported with alendronate sodium tablets. These studies showed that under low pH conditions alendronate sodium can cause esophageal irritation. No esophageal irritation occurred at pH 3.5 or higher where the drug exists primarily as the sodium salt. The animal studies also showed that alendronate sodium can exacerbate preexisting esophageal damage. Exposure of the esophageal mucosa for a prolonged period to alendronate sodium tablet can also cause mild esophageal irritation. These findings suggest that the esophageal irritation in patients taking Fosamax can be from prolonged contact with the tablet, reflux of acidic gastric contents with alendronate sodium, and exacerbation of preexisting esophageal damage. The findings also suggest that other bisphosphonates can cause esophageal injury under similar conditions.
采用体内犬模型进行动物研究，以探究阿仑膦酸钠片报告的食管不良事件的可能机制。这些研究表明，在低pH条件下，阿仑膦酸钠可引起食管刺激。在pH 3.5或更高时未发生食管刺激，此时药物主要以钠盐形式存在。动物研究还表明，阿仑膦酸钠可加重已有的食管损伤。食管黏膜长时间暴露于阿仑膦酸钠片也可引起轻度食管刺激。这些发现表明，服用福善美（Fosamax）的患者出现食管刺激可能是由于与片剂长时间接触、酸性胃内容物与阿仑膦酸钠反流以及已有的食管损伤加重。这些发现还表明，其他双膦酸盐在类似条件下也可导致食管损伤。
