Lane, M.E., Levis, K., McDonald, G.S.A. and Corrigan, O.I. (2006) Comparative assessment of two indices of drug induced permeability changes in the perfused rat intestine. International Journal of Pharmaceutics, 312 (1-2). pp. 196-199. 10.1016/j.ijpharm.2006.01.009.
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In the present study, two indices of acute intestinal permeability changes were investigated as measurements of drug induced intestinal damage. The first method was based on 14C-polyethylene glycol (PEG) 4000 permeability assessment and the second was based on histological evaluation of the intestine. The test compounds were ibuprofen, ketoprofen and naproxen and the alanine, glycine and phenylalanine amide derivatives of ibuprofen. Perfusion studies were carried out using a rat model. Post-perfusion, the gut was fixed and tissue changes were assessed and scored. Ibuprofen, ketoprofen and naproxen altered the barrier properties of the intestine to PEG 4000 with significantly higher scores (p<0.05) for gastrointestinal toxicity relative to blank buffer. For ketoprofen, PEG 4000 permeability and intestinal damage scores increased with increasing ketoprofen concentration. Ibuprofen amide derivatives did not induce significant histological damage or PEG 4000 permeability when compared with ibuprofen. A correlation coefficient of 0.91 is obtained when intestinal damage scores are plotted against PEG 4000 permeability for all compounds. Both indices are proposed as rapid and useful measures of drug induced acute intestinal damage.
|Departments, units and centres:||Department of Pharmaceutics > Department of Pharmaceutics|
|Journal or Publication Title:||International Journal of Pharmaceutics|
|Deposited By:||Library Staff|
|Deposited On:||03 Nov 2011 15:32|
|Last Modified:||03 Nov 2011 15:32|
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