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Influence of prolonged exposure of a short half life NSAIDs on gastrointestinal safety





Inflammopharmacology. 2009 Jul 8. [Epub ahead of print]


Influence of prolonged exposure of a short half life non-steroidal anti-inflammatory drugs on gastrointestinal safety.


Campanella C, Jamali F. Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Edmonton, AB, T6G 2N8, Canada.



AIMS: To test the influence of frequent concentration peaking, as occurs in multiple-dosing of non-steroidal anti-inflammatory drugs (NSAIDs) with short t (1/2), and duration of therapy of NSAIDs on gastrointestinal permeability.


METHODOLOGY: 2.5 mg/(kg 12 h) flurbiprofen was administered as repeated oral and interperitoneal (i.p) doses or as i.p. osmotic pump (once implanted to mimic long t (1/2)) for 7 days to healthy rats. Urinary excretion of (51)Cr-EDTA (days 0, 1, 4 and 7 during all regimens) and sucrose (days 0, 1 and 7 for i.p. doses) were measured as markers of gastroduodenal and intestinal permeability, respectively.


RESULTS: Both i.p. regimens elevated (51)Cr-EDTA permeability suggestive of a systemic effect. There was no significant difference between the i.p regimens in (51)Cr-EDTA permeability. The first day (51)Cr-EDTA permeability was significantly higher for the oral than for the i.p. doses suggestive of a topcal effect. The effect became less potent with time despite continuous dosing indicating adaptation for both topical and systemic effects. None of the i.p. regimen altered sucrose permeability.


CONCLUSION: NSAID's potency to increase permeability reduces with time despite continuous dosing. Topical effect following oral dosing, and not the frequent peaking differentiates regimens from each other in elevating (51)Cr-EDTA permeability. The repeated dosing rather than the magnitude of t (1/2) may influence the gut safety profile of NSAIDs.


PMID: 19585082 [PubMed - as supplied by publisher]










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