Cilostazol

證據等級: L5

預測適應症: 0 個

Cilostazol: Drug Repurposing Evaluation Report

One-Sentence Summary

Cilostazol is a phosphodiesterase III (PDE3) inhibitor historically used for the symptomatic relief of intermittent claudication in peripheral arterial disease. The TxGNN model did not return any predicted new indications for this compound in the current analysis run. No evidence pack for a repurposing direction has been assembled.

Quick Overview

Item	Content
INN	Cilostazol
DrugBank ID	DB01166
Original Indication	Intermittent claudication (peripheral arterial disease) — based on established clinical use; no local marketing authorisation data available
Predicted New Indication	None — TxGNN returned no candidates
TxGNN Prediction Score	N/A
Evidence Level	L5 (No prediction to evaluate)
UK Market Status	Not marketed (未上市)
Number of Marketing Authorisations	0
Recommended Decision	Hold

Why Was No Indication Predicted?

Cilostazol is a selective phosphodiesterase III (PDE3) inhibitor with antiplatelet and vasodilatory properties. It increases intracellular cyclic AMP (cAMP) levels in platelets and vascular smooth muscle, leading to inhibition of platelet aggregation and arterial vasodilation. It is widely approved internationally (e.g. by the FDA, EMA, and PMDA) for the treatment of intermittent claudication secondary to peripheral arterial disease.

Despite its well-characterised mechanism of action, the TxGNN knowledge-graph and deep-learning pipeline returned zero predicted indications in this run. Several factors may explain this:

No local marketing authorisation data was available — the drug has 0 licences in the input regulatory dataset, meaning the pipeline had no approved-indication anchor from which to project new disease–drug edges in the knowledge graph.
Mechanism of action data was flagged as a data gap — without a structured MOA entry linked to the knowledge graph, the model’s ability to infer pharmacological plausibility for new indications is substantially reduced.
Mapping failure — it is possible that Cilostazol’s DrugBank node (DB01166) was not successfully linked to the KG drug node during the mapping phase, preventing any prediction from being generated.

Before dismissing Cilostazol as a repurposing candidate, the data gaps identified below should be resolved and the prediction pipeline re-run.

Clinical Trial Evidence

No predicted indication was generated by TxGNN; therefore, no targeted clinical trial search was performed.

For reference, Cilostazol has been investigated in over 200 clinical trials globally (ClinicalTrials.gov), spanning peripheral arterial disease, stroke prevention, coronary artery restenosis, and heart failure. A re-run with corrected inputs may surface actionable candidates in these or related therapeutic areas.

Literature Evidence

No predicted indication was generated; therefore, no targeted literature search was performed.

UK Market Information

Cilostazol has no current marketing authorisations in the input regulatory dataset.

Note for UK context: Cilostazol was previously authorised in the EU (including the UK prior to Brexit) under the brand name Pletal (Otsuka Pharmaceutical) for the improvement of maximal and pain-free walking distances in patients with intermittent claudication. Prescribers should check the current MHRA register and BNF for the most up-to-date availability status in the United Kingdom.

Safety Considerations

Please refer to the SmPC and BNF for safety information. Report suspected adverse reactions via the Yellow Card Scheme.

Key known safety signals (from established clinical use, not from the evidence pack):

Black-box-level concern: Cilostazol is contraindicated in patients with heart failure of any severity (PDE3 inhibitors as a class have been associated with increased mortality in heart failure).
Bleeding risk: As an antiplatelet agent, cilostazol increases the risk of bleeding, particularly when co-administered with other antithrombotic agents.
Cardiac arrhythmias: Tachycardia, palpitations, and ventricular ectopy have been reported.
CYP interactions: Cilostazol is metabolised primarily by CYP3A4 and CYP2C19; strong inhibitors of either enzyme (e.g. ketoconazole, omeprazole) can significantly increase exposure and require dose reduction or avoidance.

These points are provided for clinical context only. The formal evidence pack contained no safety data (all fields returned as data gaps).

Conclusion and Next Steps

Decision: Hold

Rationale: The TxGNN model returned no predicted indications for Cilostazol. This appears to be driven by missing input data (no regulatory licence records and no structured MOA entry) rather than a genuine absence of repurposing potential. The drug has a well-understood mechanism and a broad evidence base in vascular medicine, making it a plausible candidate once data gaps are resolved.

To proceed, the following is needed:

Resolve DG001 (Blocking): Obtain SmPC/PIL warnings and contraindications from the relevant regulatory authority (MHRA or source agency) to enable Stage 1 safety screening.
Resolve DG002 (High): Populate the structured MOA field from DrugBank (PDE3 inhibitor → cAMP elevation → antiplatelet + vasodilation) so the knowledge graph can leverage mechanistic edges.
Verify KG mapping: Confirm that DrugBank ID DB01166 is correctly mapped to the TxGNN knowledge graph node for Cilostazol. Check data/processed/ mapping logs for this compound.
Re-run the prediction pipeline after resolving the above gaps:
```
uv run python scripts/run_kg_prediction.py
```
If predictions emerge, trigger evidence collectors (ClinicalTrials.gov, PubMed, DrugBank, ICTRP) for the top-ranked indication(s) and regenerate this report.

This report was generated on 2026-04-05. Results are for research purposes only and do not constitute medical advice. Any drug repurposing candidates require full clinical validation before therapeutic application.

Disclaimer

This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.