Attenuated gastropathy but not enteropathy of diclofenac-cholestyramine complex in rats

Verónica Ramírez-Alcántara, Gilberto Castañeda-Hernández, Bill Alan Rampy, Judith Aronson, Mary Treinen-Moslen

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)19-27
Number of pages9
JournalDrug Development Research
Volume64
Issue number1
DOIs
StatePublished - Jan 2005

Fingerprint

Cholestyramine Resin
Diclofenac
Rats
Anti-Inflammatory Agents
Bile Acids and Salts
Blood Proteins
Stomach
Pharmaceutical Preparations
Cytotoxicity
Mexico
Sprague Dawley Rats
Gastrointestinal Tract

Keywords

  • Cholestyramine
  • Diclofenac
  • Enteropathy
  • Flotac
  • Gastropathy

ASJC Scopus subject areas

  • Drug Discovery
  • Organic Chemistry
  • Pharmacology

Cite this

Ramírez-Alcántara, V., Castañeda-Hernández, G., Rampy, B. A., Aronson, J., & Treinen-Moslen, M. (2005). Attenuated gastropathy but not enteropathy of diclofenac-cholestyramine complex in rats. Drug Development Research, 64(1), 19-27. https://doi.org/10.1002/ddr.10417

Attenuated gastropathy but not enteropathy of diclofenac-cholestyramine complex in rats. / Ramírez-Alcántara, Verónica; Castañeda-Hernández, Gilberto; Rampy, Bill Alan; Aronson, Judith; Treinen-Moslen, Mary.

In: Drug Development Research, Vol. 64, No. 1, 01.2005, p. 19-27.

Research output: Contribution to journalArticle

Ramírez-Alcántara, V, Castañeda-Hernández, G, Rampy, BA, Aronson, J & Treinen-Moslen, M 2005, 'Attenuated gastropathy but not enteropathy of diclofenac-cholestyramine complex in rats', Drug Development Research, vol. 64, no. 1, pp. 19-27. https://doi.org/10.1002/ddr.10417
Ramírez-Alcántara, Verónica ; Castañeda-Hernández, Gilberto ; Rampy, Bill Alan ; Aronson, Judith ; Treinen-Moslen, Mary. / Attenuated gastropathy but not enteropathy of diclofenac-cholestyramine complex in rats. In: Drug Development Research. 2005 ; Vol. 64, No. 1. pp. 19-27.
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