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Gastric damage in the rat with nitrogen‐containing bisphosphonates depends on pH
Author(s) -
Ben Ma,
Gibson Gw,
Myers Wr,
Dierckman Ta,
Phipps Rj,
Smith Pn
Publication year - 2000
Publication title -
alimentary pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.308
H-Index - 177
eISSN - 1365-2036
pISSN - 0269-2813
DOI - 10.1046/j.1365-2036.2000.00816.x
Subject(s) - medicine , bisphosphonate , stomach , endocrinology , pharmacology , gastroenterology , oral administration , osteoporosis
Background: The use of nitrogen‐containing bisphosphonates (N‐BPs) has been reported to be associated with gastrointestinal intolerance. The fasted, indomethacin‐treated rat provides a model for assessing the gastrointestinal effects of these compounds. Aims: The aims of this study were to elucidate the effect of pH on N‐BP‐induced gastric damage, and to evaluate the structure–activity relationship between N‐BP anti‐resorptive and gastric effects. Methods: Fasted rats were dosed concomitantly with indomethacin (40 mg/kg, subcutaneously) and an N‐BP (pamidronate, alendronate, or risedronate at 150 or 300 mg/kg, orally), with the N‐BP dosing solutions adjusted to pH 2, 4 or 7. The aminopentane and aminohexane N‐BPs (150, 225 or 300 mg/kg, orally) were only tested at pH 4 only. Results: Nitrogen‐containing bisphosphonate‐induced gastric damage was pH‐dependent, with increased damage at increasing pH. Conclusions: Gastric damage potential did not correlate with bone anti‐resorptive effects, and the more potent anti‐resorptive N‐BPs were not necessarily more damaging to the stomach.