Gramcidin D is a heterogeneous mixture of three antibiotic compounds, gramicidins A, B and C, making up 80%, 6%, and 14% respectively all of which are obtained from the soil bacterial species Bacillus brevis and called collectively gramicidin D. Gramcidins are 15 residue peptides with alternating D and L amino acids, which assemble inside of the hydrophobic interior of the cellular lipid bilayer to form a β-helix. Active against most Gram-positive bacteria and some Gram-negative organisms, Gramicidin D is used primarily as a topical antibiotic and is also found in Polysporin ophthalmic solution.

Structure

Similar Structures

Synonyms

Bacillus brevis gramicidin D
Gramicidin
Gramicidin A
Gramicidin B
Gramicidin C
Gramicidina
Gramicidine

Mixture Products

Name	Ingredients	Dosage	Route	Labeller	Marketing Start	Marketing End
Antibiotic Cream	Gramicidin D (0.25 mg) + Polymyxin B sulfate (10000 unit)	Cream	Topical	Pharmetics (2011) Inc.	2009-12-23	Not applicable
Antibiotic Cream	Gramicidin D (0.25 mg) + Polymyxin B sulfate (10000 unit)	Cream	Topical	Canadian Custom Packaging Company	2012-03-22	Not applicable
Antibiotic Cream	Gramicidin D (0.25 mg) + Polymyxin B sulfate (10000 unit)	Cream	Topical	Technilab Pharma Inc.	1998-11-03	2005-08-05
Antibiotic Cream for Kids	Gramicidin D (0.25 mg) + Lidocaine hydrochloride (50 mg) + Polymyxin B sulfate (10000 unit)	Cream	Topical	Pharmetics (2011) Inc.	Not applicable	Not applicable
Antibiotic Cream for Kids	Gramicidin D (0.25 mg) + Lidocaine hydrochloride (50 mg) + Polymyxin B sulfate (10000 unit)	Cream	Topical	Taro Pharmaceuticals, Inc.	2009-07-30	Not applicable
Antibiotic Cream Plus Pain Relief	Gramicidin D (0.25 mg) + Lidocaine hydrochloride (40 mg) + Polymyxin B sulfate (10000 unit)	Cream	Topical	Canadian Custom Packaging Company	2012-04-09	Not applicable
Antibiotic Cream Plus Pain Relief	Gramicidin D (0.25 mg) + Lidocaine hydrochloride (50 mg) + Polymyxin B sulfate (10000 unit)	Cream	Topical	Pharmetics (2011) Inc.	2009-12-23	Not applicable
Antibiotic Cream Plus Pain Relief for Kids	Gramicidin D (0.25 mg) + Lidocaine hydrochloride (40 mg) + Polymyxin B sulfate (10000 unit)	Cream	Topical	Canadian Custom Packaging Company	2012-07-11	Not applicable
Antibiotic Drops	Gramicidin D (0.025 mg) + Polymyxin B sulfate (10000 unit)	Solution	Auricular (otic); Ophthalmic	Sandoz Canada Incorporated	2017-06-01	Not applicable
Antibiotic Ear Drops	Gramicidin D (0.025 mg) + Polymyxin B (10000 unit)	Solution / drops	Auricular (otic)	Sandoz Canada Incorporated	2017-09-01	Not applicable

International/Other Brands

Sofradex (Sanofi)

Categories

UNII

5IE62321P4

CAS number

1405-97-6

Weight

Average: 1811.253
Monoisotopic: 1810.033419343

Chemical Formula

C₉₆H₁₃₅N₁₉O₁₆

InChI Key

NDAYQJDHGXTBJL-MWWSRJDJSA-N

InChI

InChI=1S/C96H135N19O16/c1-50(2)36-71(105-79(118)48-102-93(128)80(54(9)10)103-49-117)86(121)104-58(17)84(119)113-82(56(13)14)95(130)115-83(57(15)16)96(131)114-81(55(11)12)94(129)112-78(43-62-47-101-70-33-25-21-29-66(62)70)92(127)108-74(39-53(7)8)89(124)111-77(42-61-46-100-69-32-24-20-28-65(61)69)91(126)107-73(38-52(5)6)88(123)110-76(41-60-45-99-68-31-23-19-27-64(60)68)90(125)106-72(37-51(3)4)87(122)109-75(85(120)97-34-35-116)40-59-44-98-67-30-22-18-26-63(59)67/h18-33,44-47,49-58,71-78,80-83,98-101,116H,34-43,48H2,1-17H3,(H,97,120)(H,102,128)(H,103,117)(H,104,121)(H,105,118)(H,106,125)(H,107,126)(H,108,127)(H,109,122)(H,110,123)(H,111,124)(H,112,129)(H,113,119)(H,114,131)(H,115,130)/t58-,71+,72+,73+,74+,75-,76-,77-,78-,80-,81+,82+,83-/m0/s1

IUPAC Name

(2R)-N-[(1S)-1-{[(1R)-1-{[(1S)-1-{[(1R)-1-{[(1S)-1-{[(1R)-1-{[(1S)-1-{[(1R)-1-{[(1S)-1-{[(1R)-1-{[(1S)-1-[(2-hydroxyethyl)carbamoyl]-2-(1H-indol-3-yl)ethyl]carbamoyl}-3-methylbutyl]carbamoyl}-2-(1H-indol-3-yl)ethyl]carbamoyl}-3-methylbutyl]carbamoyl}-2-(1H-indol-3-yl)ethyl]carbamoyl}-3-methylbutyl]carbamoyl}-2-(1H-indol-3-yl)ethyl]carbamoyl}-2-methylpropyl]carbamoyl}-2-methylpropyl]carbamoyl}-2-methylpropyl]carbamoyl}ethyl]-2-{2-[(2S)-2-formamido-3-methylbutanamido]acetamido}-4-methylpentanamide

SMILES

CC(C)C[C@@H](NC(=O)CNC(=O)[C@@H](NC=O)C(C)C)C(=O)N[C@@H](C)C(=O)N[C@H](C(C)C)C(=O)N[C@@H](C(C)C)C(=O)N[C@H](C(C)C)C(=O)N[C@@H](CC1=CNC2=C1C=CC=C2)C(=O)N[C@H](CC(C)C)C(=O)N[C@@H](CC1=CNC2=C1C=CC=C2)C(=O)N[C@H](CC(C)C)C(=O)N[C@@H](CC1=CNC2=C1C=CC=C2)C(=O)N[C@H](CC(C)C)C(=O)N[C@@H](CC1=CNC2=C1C=CC=C2)C(=O)NCCO

Pharmacology

Indication

For treatment of skin lesions, surface wounds and eye infections.

Associated Conditions

Superficial Eye Infections

Pharmacodynamics

Gramicidin is particularly effective against gram-positive bacteria. Because the drug is highly hemolytic, it cannot be administered internally and so is used only on the skin as a lotion or ointment. It is used primarily in the treatment of infected surface wounds, and in eye, nose, and throat infections. It is normally given with two other antibiotics (neomycin and polymixin B) as an ophthalmic solution.

Mechanism of action

Gramicidin D binds to and inserts itself into bacterial membranes (with a strong preference to gram-positive cell membranes). This results in membrane disruption and permeabilization (it acts as a channel). This leads to (i) loss of intracellular solutes (e.g., K+ and amino acids); (ii) dissipation of the transmembrane potential; (iii) inhibition of respiration; (iv) a reduction in ATP pools; and (v) inhibition of DNA, RNA, and protein synthesis, which leads to cell death.

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Additional Data Available

Adverse Effects

Comprehensive structured data on known drug adverse effects with statistical prevalence. MedDRA and ICD10 ids are provided for adverse effect conditions and symptoms.

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Additional Data Available

Contraindications

Structured data covering drug contraindications. Each contraindication describes a scenario in which the drug is not to be used. Includes restrictions on co-administration, contraindicated populations, and more.

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Additional Data Available

Blackbox Warnings

Structured data representing warnings from the black box section of drug labels. These warnings cover important and dangerous risks, contraindications, or adverse effects.

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Absorption

Not Available

Volume of distribution

Not Available

Protein binding

Not Available

Metabolism

Not Available

Route of elimination

Not Available

Half life

Not Available

Clearance

Not Available

Toxicity

Not Available

Affected organisms

Pseudomonas aeruginosa
Streptococcus pneumoniae
Streptococcus agalactiae
Neisseria meningitidis
Haemophilus influenzae
Neisseria gonorrhoeae
Escherichia coli
Staphylococcus aureus
Klebsiella
Enterobacter

Pathways

Not Available

Pharmacogenomic Effects/ADRs

Not Available

Interactions

Drug Interactions

This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.

Drug	Interaction
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(R)-warfarin	The risk or severity of bleeding can be increased when Gramicidin D is combined with (R)-warfarin.
(S)-Warfarin	The risk or severity of bleeding can be increased when Gramicidin D is combined with (S)-Warfarin.
4-hydroxycoumarin	The risk or severity of bleeding can be increased when Gramicidin D is combined with 4-hydroxycoumarin.
Abemaciclib	The serum concentration of Abemaciclib can be increased when it is combined with Gramicidin D.
Acebutolol	The serum concentration of Acebutolol can be increased when it is combined with Gramicidin D.
Acenocoumarol	The risk or severity of bleeding can be increased when Gramicidin D is combined with Acenocoumarol.
Acetaminophen	The serum concentration of Acetaminophen can be increased when it is combined with Gramicidin D.
Acetyldigoxin	Gramicidin D may decrease the excretion rate of Acetyldigoxin which could result in a higher serum level.
Acetylsalicylic acid	The serum concentration of Acetylsalicylic acid can be increased when it is combined with Gramicidin D.
Afatinib	The serum concentration of Afatinib can be increased when it is combined with Gramicidin D.

Additional Data Available

Extended Description

Extended description of the mechanism of action and particular properties of each drug interaction.

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Severity

A severity rating for each drug interaction, from minor to major.

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Evidence Level

A rating for the strength of the evidence supporting each drug interaction.

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Action

An effect category for each drug interaction. Know how this interaction affects the subject drug.

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Food Interactions

Not Available

References

Synthesis Reference

U.S.Patent 2,534,541.

General References

Ketchem RR, Lee KC, Huo S, Cross TA: Macromolecular structural elucidation with solid-state NMR-derived orientational constraints. J Biomol NMR. 1996 Jul;8(1):1-14. [PubMed:8810522]
Townsley LE, Tucker WA, Sham S, Hinton JF: Structures of gramicidins A, B, and C incorporated into sodium dodecyl sulfate micelles. Biochemistry. 2001 Oct 2;40(39):11676-86. [PubMed:11570868]
Burkhart BM, Gassman RM, Langs DA, Pangborn WA, Duax WL, Pletnev V: Gramicidin D conformation, dynamics and membrane ion transport. Biopolymers. 1999;51(2):129-44. [PubMed:10397797]

External Links

KEGG Drug: D04369
PubChem Compound: 45267103
PubChem Substance: 46507412
ChemSpider: 24623445
ChEMBL: CHEMBL557217
Therapeutic Targets Database: DAP001327
PharmGKB: PA449808
Wikipedia: Gramicidin_D

ATC Codes

R02AB30 — Gramicidin

MSDS

Download (71.9 KB)

Clinical Trials

Clinical Trials

Phase	Status	Purpose	Conditions	Count
3	Unknown Status	Treatment	Hordeolum	1
Not Available	Withdrawn	Prevention	Blood Stream Infections / Skin Diseases, Infectious	1

Pharmacoeconomics

Manufacturers

Not Available

Packagers

Johnson & Johnson Healthcare
Monarch Pharmacy
Professional Co.

Dosage forms

Form	Route	Strength
Solution / drops	Auricular (otic)
Solution / drops	Ophthalmic
Solution	Ophthalmic
Solution	Auricular (otic); Ophthalmic
Liquid	Ophthalmic
Liquid	Auricular (otic); Ophthalmic
Solution / drops	Auricular (otic); Ophthalmic
Ointment	Topical
Solution / drops	Topical
Ointment	Auricular (otic); Ophthalmic
Spray	Nasal
Cream	Topical

Prices

Unit description	Cost	Unit
Gramicidin d powder	240.0USD	g
Neosporin gu irr 40 mg/ml amp	23.12USD	ml
Neosporin + pain relief cream	0.32USD	g

DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.

Patents

Not Available

Properties

State

Liquid

Experimental Properties

Property	Value	Source
melting point (°C)	229 °C	Not Available

Predicted Properties

Property	Value	Source
Water Solubility	0.0039 mg/mL	ALOGPS
logP	4.38	ALOGPS
logP	5.96	ChemAxon
logS	-5.7	ALOGPS
pKa (Strongest Acidic)	11.56	ChemAxon
Physiological Charge	0	ChemAxon
Hydrogen Acceptor Count	16	ChemAxon
Hydrogen Donor Count	20	ChemAxon
Polar Surface Area	519.89 Å²	ChemAxon
Rotatable Bond Count	50	ChemAxon
Refractivity	492.33 m³·mol^-1	ChemAxon
Polarizability	194.73 Å³	ChemAxon
Number of Rings	8	ChemAxon
Bioavailability	0	ChemAxon
Rule of Five	No	ChemAxon
Ghose Filter	No	ChemAxon
Veber's Rule	No	ChemAxon
MDDR-like Rule	Yes	ChemAxon

Predicted ADMET features

Not Available

Spectra

Mass Spec (NIST): Not Available
Spectra: Not Available

Taxonomy

Description: This compound belongs to the class of organic compounds known as polypeptides. These are peptides containing ten or more amino acid residues.
Kingdom: Organic compounds
Super Class: Organic Polymers
Class: Polypeptides
Sub Class: Not Available
Direct Parent: Polypeptides
Alternative Parents: Peptides / Leucine and derivatives / Valine and derivatives / N-acyl-alpha amino acids and derivatives / Tryptamines and derivatives / N-formyl-alpha amino acids / Alpha amino acid amides / Alanine and derivatives / 3-alkylindoles / N-acylethanolamines
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Substituents: Polypeptide / Alpha peptide / Leucine or derivatives / Valine or derivatives / N-acyl-alpha amino acid or derivatives / Alpha-amino acid amide / N-formyl-alpha-amino acid / N-formyl-alpha amino acid or derivatives / Triptan / Alanine or derivatives
show 29 more
Molecular Framework: Aromatic heteropolycyclic compounds
External Descriptors: Not Available

Transporters

Details1. P-glycoprotein 1

Kind: Protein
Organism: Humans
Pharmacological action: Unknown
Actions: Inhibitor

General Function: Xenobiotic-transporting atpase activity
Specific Function: Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells.
Gene Name: ABCB1
Uniprot ID: P08183
Uniprot Name: Multidrug resistance protein 1
Molecular Weight: 141477.255 Da

References

Nagy H, Goda K, Fenyvesi F, Bacso Z, Szilasi M, Kappelmayer J, Lustyik G, Cianfriglia M, Szabo G Jr: Distinct groups of multidrug resistance modulating agents are distinguished by competition of P-glycoprotein-specific antibodies. Biochem Biophys Res Commun. 2004 Mar 19;315(4):942-9. [PubMed:14985103]

Drug created on June 13, 2005 07:24 / Updated on November 02, 2019 00:16

Gramicidin D

Identification

Structure for Gramicidin D (DB00027)

Pharmacology

Interactions

References

Clinical Trials

Pharmacoeconomics

Properties

Spectra

Taxonomy

Transporters

References