Title page for ETD etd-04052000-18260052


Type of Document Master's Thesis
Author Ward, Deborah Marie
Author's Email Address doctor4dogs@aol.com
URN etd-04052000-18260052
Title Effect of Dosing Interval on the Efficacy of Misoprostol in the Prevention of Aspirin-Induced gastric Injury in the Dog
Degree Master of Science
Department Veterinary Medical Sciences
Advisory Committee
Advisor Name Title
Leib, Michael S. Committee Chair
Duncan, Robert B. Jr. Committee Member
Johnston, Spencer A. Committee Member
Monroe, William Edward Committee Member
Keywords
  • NSAIDs
  • dogs
  • gastric ulceration
  • Aspirin
  • misoprostol
Date of Defense 2000-03-27
Availability unrestricted
Abstract
The effect of reduced frequency of administration of misoprostol on its ability to prevent aspirin-induced gastric injury was evaluated. Twenty-four random-source dogs were divided into 4 groups which received aspirin and misoprostol as follows: Group I, 25 mg/kg aspirin PO TID and placebo PO TID; Group II, 25 mg/kg aspirin PO TID and misoprostol 3 ug/kg PO TID; Group III, 25 mg/kg aspirin PO TID, misoprostol 3 ug/kg PO BID and placebo PO QD; and Group IV, 25 mg/kg aspirin PO TID, misoprostol 3 ug/kg PO QD and placebo PO BID for 28 days. Groups were stratified to contain an equal number of dogs positive or negative for Helicobacter spp. based on results of 'CLO test'.

Gastroscopy was performed on days -9, 5, 14 and 28. Each region of the stomach was evaluated separately and visible lesions were scored on a scale of 1 (submucosal hemorrhage) to 11 (perforating ulcer). The scores for each region were summed and the median total score for each group at each day and median total score within each group between days was compared using a Kruskal-Wallis test.

No difference in total score was identified between Group I and IV on any day. Median total scores for Groups II and III were significantly (p < 0.05) lower compared to Groups I and IV on day 5. Significant difference was observed on Day 14 between the total score of Group III and Group IV. Group III had a significantly lower score (p < 0.05) than Groups I, II and IV on day 28. Gastric erosions were present in all groups in the study. This study suggests that misoprostol 3 ug/kg PO BID dosing is as effective as misoprostol 3 ug/kg PO TID dosing at preventing aspirin-induced gastric injury in this model. However, misoprostol 3 ug/kg PO TID dosing was less effective in preventing aspirin-induced gastric injury on days 14 and 28 than in previous studies. The lack of efficacy of TID dosing on days 14 and 28 may be related to higher salicylate concentrations in Group II dogs or individual variation within the small study population.

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