PeptideTrace
ApprovedPolypeptide Antibiotic (Topical/Ophthalmic)

Gramicidin

Neosporin Ophthalmic (combination)

A

Evidence Grade A — Regulatory approved. 3714 published studies. 5 registered clinical trials.

5 trials3,714 studiesUSEUCA

Licensed Indications

  • Superficial Eye Infections

User Experience Reports

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Overview

Gramicidin is a topical antibiotic peptide found in combination eye drops such as Neosporin Ophthalmic Solution. It is far too toxic for systemic use but provides effective gram-positive bacterial coverage when applied directly to the eye surface. Historically, gramicidin is significant as one of the very first antibiotics ever discovered — its success in animals in 1939 was a key catalyst for the development of penicillin.

Research Activity

3,714studies
Human 515
Animal 779
In-vitro 225
Reviews 145

3,714 published studies: 515 human, 779 animal, 225 in-vitro, 145 reviews

Regulatory Status

US
FDA-approved(FDA)
EU
Not authorised by EMA(EMA)
CA
Health Canada approved(Health Canada)

Legal Status

USPrescription drug (Rx)
EUNot applicable (not authorised)
CAPrescription drug

Summary

Gramicidin is available in combination ophthalmic products such as Neosporin Ophthalmic Solution (with neomycin and polymyxin B), approved 1949. It provides gram-positive bacterial coverage in these combinations.

Gramicidin's significance extends well beyond its clinical use. It was the first antibiotic shown to cure systemic bacterial infections in animals (1939), and the demonstration that a natural substance could fight infection in living organisms was a key catalyst for the development of penicillin. In basic science, gramicidin remains the most-studied ion channel peptide, providing foundational understanding of how molecules transport ions across membranes.

Mechanism of Action

Gramicidin has an extraordinary molecular mechanism that has made it one of the most studied peptides in biophysics. Its alternating D- and L-amino acids allow it to form a helix that spans the bacterial cell membrane. Two gramicidin molecules meet head-to-head inside the membrane, creating a tiny channel that allows ions to flood through uncontrollably — approximately six million ions per second. This destroys the bacterium's ability to maintain its internal chemistry, killing the cell. The channel is too toxic for systemic use but effective when applied topically.

Research Summary

Gramicidin's clinical evidence is entirely historical, predating modern trial standards by decades. Its safety and effectiveness as a topical ophthalmic antibiotic are supported by prolonged clinical experience rather than randomised controlled trials. The haemolytic (blood cell-destroying) activity that makes it unsuitable for systemic use is well documented. Outside clinical use, gramicidin is one of the most studied molecules in biophysics — the tiny ion channels it forms in cell membranes have been the subject of over 50 years of fundamental research. More recently, gramicidin's ability to accumulate in mitochondria and disrupt energy production has attracted interest in anticancer research, with laboratory screening of thousands of gramicidin variants aimed at reducing toxicity while retaining anti-tumour activity.

Clinical Trials

NCT06859281Phase IRecruiting

Safety, Tolerability, and Pharmacokinetic Profile of Grammidin, a Metered Dose Topical Spray in Healthy Volunteers

Valenta Pharm JSCEndpoint: Pharmacokinetics - CmaxCompletion: 2026-12-01
NCT06857890Phase IRecruiting

Safety, Tolerability, and Pharmacokinetic Profile of Grammidin With Anesthetic, a Metered Dose Topical Spray in Healthy Volunteers

Valenta Pharm JSCEndpoint: Pharmacokinetics - CmaxCompletion: 2026-12-01
NCT06843018Phase IIRecruiting

Study to Evaluate the Efficacy and Safety of Different Doses of Graminidin With Anesthetic, a Metered Dose Topical Spray, in the Treatment of Acute Infectious and Inflammatory Pharyngeal Diseases Compared With Drug Septolete Total, Lozenges

Valenta Pharm JSCEndpoint: Combined primary efficacy endpoint: VAS + TPACompletion: 2026-12-31
NCT04323475Phase IUnknown

Phage Therapy for the Prevention and Treatment of Wound Infections in Burned Patients

Precisio Biotix Therapeutics, Inc.Endpoint: Incidence of Treatment-Emergent Adverse Events coded by MedDraCompletion: 2023-08-01
NCT01524744Phase IIUnknown

A Randomized Clinical Trial of the Effect of Pimecrolimus Cream 1% Compared With Topical Corticosteroid in Treatment of Erosive Oral Lichen Planus

Mashhad University of Medical SciencesEndpoint: signs of oral lichen planusCompletion: 2012-12-01
View all 5 trials on ClinicalTrials.gov →

Regulatory Timeline

1996
Regulatory

FDA ORIG 1

1997
Regulatory

FDA SUPPL 1

1998
Regulatory

FDA SUPPL 2

1998
Regulatory

FDA SUPPL 3

1998
Regulatory

Health Canada Market Authorisation

1998
Regulatory

FDA SUPPL 4

1998
Regulatory

FDA SUPPL 5

1999
Regulatory

FDA SUPPL 6

1999
Regulatory

FDA SUPPL 7

2000
Regulatory

FDA SUPPL 9

2000
Regulatory

FDA SUPPL 8

2000
Regulatory

FDA SUPPL 10

2001
Regulatory

FDA SUPPL 11

2001
Regulatory

FDA SUPPL 12

2001
Regulatory

FDA SUPPL 14

2001
Regulatory

FDA SUPPL 13

Related Compounds

Corticotropin

Approved
Repository ACTH Preparation

Corticotropin is marketed as H.P. Acthar Gel (currently ANI Pharmaceuticals). It carries approximately 19 FDA-labelled indications including infantile spasms (its strongest evidence base), nephrotic syndrome, multiple sclerosis relapses, and rheumatic disorders. Acthar Gel has been at the centre of major pricing and legal controversies. The price rose from approximately $40 per vial in 2001 to over $40,000, driven by successive acquisitions and orphan-like positioning despite broad labelling. The former manufacturer Mallinckrodt agreed to a $260 million settlement over antitrust concerns. Clinically, the strongest evidence supports its use in infantile spasms, where it is considered a first-line treatment. For most other indications, debate continues over whether it offers meaningful advantages over far less expensive oral corticosteroids.

Enfuvirtide

Approved
HIV Fusion Inhibitor (Peptide)

Enfuvirtide is marketed as Fuzeon (approved March 2003). It requires twice-daily subcutaneous injections, and injection-site reactions occur in nearly all patients (98%). In clinical trials (TORO-1 and TORO-2), enfuvirtide combined with an optimised background regimen achieved significantly greater viral suppression than background regimen alone in treatment-experienced patients. Enfuvirtide represented a major advance when HIV drug resistance was a more pressing clinical challenge, but its use has declined substantially with the arrival of more convenient oral antiretrovirals. The twice-daily injection burden, injection-site reactions, high cost, and complex manufacturing (it is one of the largest synthetic peptides manufactured at scale) have limited its role to a last-resort option for patients with highly resistant HIV.

Vancomycin

Approved
Glycopeptide Antibiotic

Vancomycin is marketed as Vancocin and Firvanq (approved 1958, with oral solution Firvanq approved 2018). It is the standard treatment for serious MRSA infections (bloodstream infections, endocarditis, pneumonia, bone infections) and is first-line for severe C. difficile colitis. Vancomycin requires therapeutic drug monitoring — blood levels must be checked regularly to ensure the dose is effective without causing kidney damage or hearing loss. The rise of vancomycin-resistant enterococci (VRE) and occasional vancomycin-intermediate S. aureus (VISA) strains represent ongoing challenges. Despite being nearly 70 years old, vancomycin remains irreplaceable for many serious infections, though newer alternatives like daptomycin and the lipoglycopeptides offer advantages in specific settings.