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Attenuated gastropathy but not enteropathy of diclofenac–cholestyramine complex in rats
Author(s) -
RamírezAlcántara Verónica,
CastañedaHernández Gilberto,
Alan Rampy Bill,
Aronson Judith F.,
TreinenMoslen Mary
Publication year - 2005
Publication title -
drug development research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.582
H-Index - 60
eISSN - 1098-2299
pISSN - 0272-4391
DOI - 10.1002/ddr.10417
Subject(s) - cholestyramine , diclofenac , enteropathy , medicine , analgesic , pharmacology , gastroenterology , stomach , chemistry , endocrinology , disease , cholesterol
Diclofenac is a nonsteroidal anti‐inflammatory drug (NSAID) widely prescribed for pain and inflammation. Theoretically, the gastrointestinal (GI) complications of diclofenac could be minimized by administering a diclofenac resinate formulation, such as Flotac, where GI mucosal contact with free NSAID is minimized by its complexing with the cholestyramine resin. The objective of the present study was to investigate the influence of cholestyramine co‐treatment on diclofenac enteropathy in fed rats and diclofenac gastropathy in fasted rats. Male Sprague‐Dawley rats were gavaged with diclofenac (50 mg/kg), diclofenac (50 mg/kg) plus cholestyramine (50 mg/kg), or an equivalent amount of Flotac, a 1:1 wt/wt mixture of diclofenac and cholestyramine presently used in human therapeutics in Mexico. Ulceration of the GI tract, serum proteins, and bile salts were assessed at 3, 12, or 24 h. Cholestyramine alone produced no detectable alterations in small intestinal integrity or serum bile salts levels. Fed rats given Flotac or diclofenac plus cholestyramine showed patterns of small intestinal ulceration and serum protein decline that were similar to rats given only diclofenac. Thus, no influence on enteropathy was detected. In contrast, fasted rats given Flotac showed a modest reduction in the number and length of gastric lesions compared to rats given diclofenac. The observed attenuation of gastric lesions with Flotac is consistent with a role for direct cytotoxicity in NSAID gastropathy. Drug Dev. Res. 64:19–27, 2005. © 2005 Wiley‐Liss, Inc.