Metoclopramide
| 證據等級: L5 | 預測適應症: 5 個 |
目錄
Metoclopramide: From No Local Approval to Predicted Gastric Ulcer Use
One-Sentence Summary
Metoclopramide is a dopamine D2 antagonist / 5‑HT4 agonist prokinetic agent that is not currently marketed in this jurisdiction (no approved indication on file locally). The TxGNN model predicts it may be effective for Gastric Ulcer (disease), with 2 clinical trials and 20 publications returned by the evidence search — though most of this evidence is decades-old animal/mechanistic work, and the evidence pack’s own mechanistic assessment flags the biological link as weak.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Not on file — drug is not currently marketed in this jurisdiction (0 licenses) |
| Predicted New Indication | Gastric Ulcer (disease) |
| TxGNN Prediction Score | 99.93% |
| Evidence Level | L4 |
| US Market Status | Not Marketed |
| Number of NDAs | 0 |
| Recommended Decision | Hold |
Why is This Prediction Reasonable?
Detailed mechanism-of-action data was not returned for this evidence pack (open data gap DG002). Based on the pharmacology cited in the evidence pack’s own repurposing rationale, metoclopramide acts as a dopamine D2 antagonist and 5‑HT4 agonist with prokinetic effects — it promotes gastric emptying and raises lower esophageal sphincter tone. It is not an acid suppressant or a mucosal protectant.
This matters because standard gastric ulcer therapy targets acid suppression (PPIs, H2 blockers) or H. pylori eradication — mechanisms metoclopramide does not share. The evidence pack’s rationale explicitly notes this mismatch: 1970s–80s animal studies (rats, guinea pigs) on gastric ulcer protection show inconsistent results, and several are protective via non-acid-related mechanisms (improved gastric drainage, reduced pyloric reflux) rather than mucosal healing per se.
In short, the very high TxGNN score is not well corroborated by a coherent mechanistic story or by controlled clinical evidence — the biological plausibility for this specific indication is weak, which is reflected in the “Hold” recommendation already assigned in the evidence pack.
Clinical Trial Evidence
| Trial Number | Phase | Status | Enrollment | Key Findings |
|---|---|---|---|---|
| NCT05746377 | Phase 4 | Unknown | 60 | Tests whether metoclopramide premedication before endoscopy improves GI-wall visibility and reduces need for repeat endoscopy/IR/surgery in upper GI bleeding — this is a premedication/visualization study, not a gastric-ulcer treatment trial. Graded low relevance (C); status not updated since the 2024 completion date. |
| NCT03747107 | N/A | Completed | 19 | Pharmacist-led prescribing-safety quality-improvement programme in Scottish primary care. Unrelated to gastric ulcer treatment; weak co-occurrence match (graded C). |
Literature Evidence
20 publications were returned; the 5 below are the only ones with a completed study-type classification in the evidence pack. The remaining 15 are older, unclassified physiology/case reports and are not detailed here to avoid overstating their relevance.
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 16807979 | 2006 | RCT (small, surgical premedication) | Yonsei Medical Journal | IV metoclopramide + ranitidine reduced preoperative gastric contents vs. saline in day-case laparoscopic gynecologic surgery (n=20/group). A perioperative RCT, not a gastric-ulcer treatment study. |
| 6336644 | 1983 | Review | Annals of Internal Medicine | General pharmacology review; metoclopramide’s established roles are as an antiemetic (chemotherapy-induced vomiting) and GI prokinetic, not an acid-suppressive ulcer therapy. |
| 19225 | 1977 | Review | Drugs | Era-appropriate review of gastric/duodenal ulcer drug therapy; metoclopramide appears only as a motility adjunct, predating the modern PPI/H2-blocker/H. pylori treatment paradigm. |
| 2730234 | 1989 | Animal study | Arch Int Pharmacodyn Ther | In rats, metoclopramide (20–50 mg/kg) showed an ulcer-protective effect in aspirin-induced and pylorus-ligated models, comparable to ranitidine. Preclinical only. |
| 6436177 | 1984 | Animal study | Indian J Physiol Pharmacol | In guinea pigs, metoclopramide protected against experimentally-induced gastric ulceration without changing acid secretion — suggesting a drainage/motility-based mechanism rather than mucosal healing. Preclinical only. |
Market Information
No approved product licenses are on file — metoclopramide is currently not marketed in this jurisdiction (0 of 0 NDAs).
Safety Considerations
Please refer to the package insert for safety information.
Conclusion and Next Steps
Decision: Hold
Rationale:
- The TxGNN score is very high (99.93%), but the supporting evidence is almost entirely decades-old preclinical/animal work and tangentially related trials (endoscopy premedication, unrelated QI programme) — no controlled trial directly tests metoclopramide for gastric ulcer healing.
- The evidence pack’s own mechanistic rationale flags weak biological plausibility: metoclopramide is a prokinetic agent, not an acid suppressant or mucosal protectant, which is the established mechanism class for this indication.
- The drug has no local market license (0 NDAs, not marketed), so there is no regulatory/safety file to begin a formal S1 review.
To proceed, the following is needed:
- Resolve DG001 (Blocking): obtain official label warnings/contraindications before any safety evaluation
- Resolve DG002: confirm mechanism of action via DrugBank API to properly assess mechanistic relevance
- Clarify local licensing/import status given the current 0-NDA position
- Identify a modern, adequately powered RCT testing metoclopramide specifically for gastric ulcer healing (not motility/premedication surrogate endpoints) before advancing beyond Hold
- Complete the outstanding DDI query (currently
not_found)Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.