Paromomycin
| 證據等級: L5 | 預測適應症: 8 個 |
目錄
- Paromomycin
- Paromomycin (DB01421): Original Indication Unclear → Idiopathic Copper-Associated Cirrhosis (Low-Confidence Candidate)
Paromomycin (DB01421): Original Indication Unclear → Idiopathic Copper-Associated Cirrhosis (Low-Confidence Candidate)
One-Sentence Summary
Paromomycin’s approved indication could not be determined from this evidence pack (no Taiwan license records, no original indication text on file), though the underlying rationale text describes it as a non-absorbable aminoglycoside antibiotic used against amoebiasis/leishmaniasis. The TxGNN model’s top prediction is Idiopathic Copper-Associated Cirrhosis, but this shares an identical score with four other unrelated hepatic/vascular disorders (ranks 2–5), and the model’s own rationale text flags this cluster as a likely false positive driven by liver-disease node embedding similarity, not a genuine mechanistic signal. No clinical trials or literature support any of the top-ranked predictions; the only indication with any literature backing (peritonitis, rank 8) has weak, indirect evidence only.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Not available — no Taiwan license records or approved indication text on file for this drug |
| Predicted New Indication | Idiopathic Copper-Associated Cirrhosis (rank 1; tied in score with 4 other hepatic/vascular diseases at ranks 2–5) |
| TxGNN Prediction Score | 99.90% |
| Evidence Level | L5 (model prediction only, no supporting studies) |
| Market Status (Taiwan) | Not Marketed |
| Number of Licenses | 0 |
| Recommended Decision | Hold |
Why is This Prediction Reasonable?
The formal original_moa field is marked as a data gap. However, the evidence pack’s own rationale text describes paromomycin as a non-absorbable aminoglycoside antibiotic that acts by inhibiting 30S ribosomal protein synthesis in susceptible organisms, giving it antiamoebic and antileishmanial activity.
There is no identifiable mechanistic pathway connecting this antimicrobial action to the pathophysiology of the top five predicted indications (copper-associated cirrhosis, hepatoportal sclerosis, hepatopulmonary syndrome, familial noncirrhotic portal hypertension, primary portal vein thrombosis). All five diseases sit in the same “liver disease” node neighborhood and share an identical TxGNN score, which strongly suggests the ranking reflects knowledge-graph embedding clustering rather than a true drug–disease mechanistic relationship.
Two additional findings work against pursuing this candidate further:
- Rank 7 (acute urate nephropathy) shows a negative mechanistic signal — aminoglycosides, including paromomycin, carry known nephrotoxicity risk (PMID 4293095), making this indication counter-indicated rather than promising.
- Rank 8 (peritonitis) has the only literature support in the pack, but it is indirect (amoebic colitis can rarely progress to amoebic peritonitis) and the bulk of the cited literature is unrelated in-vitro/leishmaniasis resistance research retrieved as keyword noise, not peritonitis-specific evidence.
Given this, none of the eight predicted indications currently has a defensible mechanistic or clinical rationale for repurposing.
Clinical Trial Evidence
Currently no related clinical trials registered for the top-ranked predicted indication (Idiopathic Copper-Associated Cirrhosis).
Literature Evidence
Currently no related literature available for the top-ranked predicted indication (Idiopathic Copper-Associated Cirrhosis).
(Note: among all 8 candidates evaluated, only rank 8 — peritonitis — has any literature evidence, and it is indirect/weak; see rationale above.)
Market Information
No marketing authorization records are available — this drug is currently not marketed in the evaluated jurisdiction (0 licenses on file).
Safety Considerations
Please refer to the package insert for safety information.
Note: A Blocking data gap (DG001) has been identified — the local regulatory label/warnings and contraindications could not be retrieved, which by itself prevents this candidate from advancing to Stage 1 safety review regardless of efficacy evidence.
Conclusion and Next Steps
Decision: Hold
Rationale: All eight TxGNN-predicted indications lack mechanistic plausibility or clinical/trial evidence; the top five appear to be a knowledge-graph embedding artifact rather than a genuine signal, and one (acute urate nephropathy) is actively counter-indicated by paromomycin’s known nephrotoxicity. Separately, a Blocking safety data gap (missing label/warnings) prevents any candidate from this drug from entering safety review at this time.
To proceed, the following is needed:
- Retrieve official label warnings/contraindications (DG001, Blocking) — required before any Stage 1 safety review
- Obtain confirmed mechanism of action data from DrugBank (DG002, High)
- If pursuing further, prioritize independent verification of the peritonitis (rank 8) signal with peritonitis-specific literature/trial searches, since it is the only candidate with any topical evidence — current searches returned largely off-target leishmaniasis/in-vitro studies
- Given the near-zero mechanistic basis, this drug is a low-priority candidate for repurposing pending materially stronger new evidence
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.