Evaluation of gastrointestinal toxicity of ibuprofen using surrogate markers in rats: effect of formulation and route of administration.
Bibliographic record
Abstract
OBJECTIVE: To elucidate the mechanism of gastrointestinal (GI) toxicity of ibuprofen and to examine the effect of altered site of drug release using gastroduodenal and intestinal permeability tests in the rat model. METHODS: Adult male Sprague-Dawley rats were administered (n = 6 per group) either: (1) 100 mg/kg immediate or sustained release ibuprofen; (2) 100 mg/kg immediate release and ibuprofen lysinate; or (3) 100 mg/kg or 200 mg/kg ibuprofen po or s.c. Upper and lower GI permeability as a surrogate marker of toxicity were determined at pre-determined times using the urinary excretion of orally administered sucrose and 51Cr-EDTA permeability probes, respectively. RESULTS: Ibuprofen administration resulted in a dose-dependent increase in both upper and lower permeability of the GI tract. Both immediate and sustained release preparations of ibuprofen increased upper and lower GI permeability with no shift of toxicity to the site of drug release. Ibuprofen lysinate also induced significant increased upper and lower GI permeability comparable to immediate release ibuprofen. Oral doses were not more toxic than s.c. doses. CONCLUSION: Ibuprofen-induced increased GI permeable appears to be independent of the type of formulation and route of administration. This indicates that, contrary to some other nonsteroidal anti-inflammatory drugs, ibuprofen's effect on GI permeability is mainly systemic and the direct local effect contributes minimally to its overall GI toxicity. Ibuprofen may be a suitable candidate for sustained release formulations since its effect may be prolonged without the danger of a shift of side effect from the upper to the lower GI tract.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.000 |
| Meta-epidemiology (narrow) | 0.002 | 0.001 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.000 | 0.001 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.002 |
| Insufficient payload (model declined to judge) | 0.002 | 0.001 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".