Prucalopride
| Evidence Level: L5 | Predicted Indications: 10 |
Table of Contents
Prucalopride: From Constipation to Hypoalphalipoproteinemia
One-Sentence Summary
Prucalopride is a selective 5-HT4 receptor agonist (a gut prokinetic) originally used to treat chronic constipation. The TxGNN model predicts it may be effective for hypoalphalipoproteinemia (low HDL cholesterol), but no clinical trials and no publications currently support this prediction, so it rests on the model score alone.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Constipation disorder (from the knowledge graph; the Singapore licence records contain no indication text) |
| Predicted New Indication | Hypoalphalipoproteinemia |
| TxGNN Prediction Score | 99.82% |
| Evidence Level | L5 |
| Singapore Market Status | ✓ Marketed |
| Number of Registrations | 2 |
| Recommended Decision | Hold |
Why is This Prediction Reasonable?
Currently, detailed mechanism of action data is not available in the data compiled for this report. Based on known information, prucalopride is a selective 5-HT4 receptor agonist that promotes gut motility, and its efficacy in constipation is established.
For hypoalphalipoproteinemia, no mechanistic link can be established from the available data. No known pathway connects gut 5-HT4 agonism to HDL metabolism. The high score (99.82%) is a knowledge-graph prediction only and should be treated as a hypothesis, not evidence.
Other top-ranked predictions are similarly unsupported (for example homozygous familial hypercholesterolemia, duodenal ulcer, oral candidiasis, strongyloidiasis and HIV infection). The only predictions with any related literature are amyloidosis and primary amyloidosis. There, a prokinetic might relieve gut dysmotility symptoms such as pseudo-obstruction, but this would not treat the underlying disease. Those two are better framed as research questions.
Clinical Trial Evidence
Currently no related clinical trials registered.
Literature Evidence
Currently no related literature available for hypoalphalipoproteinemia.
For reference, the two papers retrieved for the amyloidosis predictions (rank 6 and rank 9) are listed below. Neither shows prucalopride efficacy.
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 40376135 | 2025 | Case report | Cureus | Amyloidosis presenting as chronic intestinal pseudo-obstruction in a 61-year-old man after multiple unrevealing laparotomies |
| 34231480 | 2021 | Cohort | Turk J Gastroenterol | Specific GI motility disorders (gastroparesis, CIPO, colonic inertia) are often misdiagnosed as functional GI disorders in the early stage |
Singapore Market Information
| Authorization Number | Product Name | Dosage Form | Approved Indication |
|---|---|---|---|
| SIN14103P | Resolor Film-coated Tablet 1 mg | Tablet, film coated | Not available in the compiled data |
| SIN14104P | Resolor Film-coated Tablet 2 mg | Tablet, film coated | Not available in the compiled data |
Both licences are valid single-ingredient oral products from Janssen Cilag S.p.A.
Safety Considerations
- Disease-level contraindications (knowledge graph, not label text): ulcerative colitis, inflammatory bowel disease, intestinal perforation.
- Drug Interactions: 98 interactions were identified in total. The listed examples include:
- Moderate: anticholinergic or antimuscarinic agents (aclidinium, atropine, benztropine, biperiden, clidinium, glycopyrronium, hyoscyamine) and hormonal contraceptive components (levonorgestrel, norethisterone, ethinylestradiol).
- Minor: nifedipine, afatinib, alpelisib, amiodarone, cobicistat, captopril, diltiazem, spironolactone, carvedilol, conivaptan.
Please refer to the package insert for full warnings and contraindications.
Conclusion and Next Steps
Decision: Hold
Rationale: The prediction for hypoalphalipoproteinemia has no clinical trials, no literature and no plausible mechanistic link (Evidence Level L5). A high model score alone is not enough to justify moving forward.
To proceed, the following is needed:
- A plausible mechanistic rationale connecting 5-HT4 agonism to HDL/lipid metabolism, plus mechanism of action data
- Preclinical or clinical evidence in hypoalphalipoproteinemia
- Package insert warnings and contraindications from HSA, which are required for safety screening
- Approved indication text for the Singapore licences
- Optionally, a separate evaluation of the amyloidosis-related GI dysmotility question as a symptom-management research question
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.