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

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Abstract

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 51Cr-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 51Cr-EDTA permeability suggestive of a systemic effect. There was no significant difference between the i.p regimens in 51Cr-EDTA permeability. The first day 51Cr-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 51Cr-EDTA permeability. The repeated dosing rather than the magnitude of t 1/2 may influence the gut safety profile of NSAIDs.

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Acknowledgments

This work was supported by a Canadian Institute of Health Research grant.

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Author notes

  1. Corinne Campanella

    Present address: Biovail Contract Research, Toronto, ON, M1L 4S4, Canada

Authors and Affiliations

  1. Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Edmonton, AB, T6G 2N8, Canada

    Corinne Campanella & Fakhreddin Jamali

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  1. Corinne Campanella
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  2. Fakhreddin Jamali
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Correspondence to Fakhreddin Jamali.

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Campanella, C., Jamali, F. Influence of prolonged exposure of a short half life non-steroidal anti-inflammatory drugs on gastrointestinal safety. Inflammopharmacol 17, 205–210 (2009). https://doi.org/10.1007/s10787-009-0007-y

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  • DOI: https://doi.org/10.1007/s10787-009-0007-y

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