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Gastric damage in the rat with nitrogen-containing bisphosphonates depends on pH
Article first published online: 24 DEC 2001
DOI: 10.1046/j.1365-2036.2000.00816.x
1365-2036/asset/cover.gif?v=1&s=d621428d7905f55dc6cbe431b6da6a6c8f16399c "Alimentary Pharmacology & Therapeutics")
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How to Cite
Blank, Gibson, Myers, Dierckman, Phipps and Smith (2000), Gastric damage in the rat with nitrogen-containing bisphosphonates depends on pH. Alimentary Pharmacology & Therapeutics, 14: 1215–1223. doi: 10.1046/j.1365-2036.2000.00816.x
Publication History
- Issue published online: 24 DEC 2001
- Article first published online: 24 DEC 2001
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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.